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Review • J. Braz. Chem. Soc. 35 (7) • 2024 • https://doi.org/10.21577/0103-5053.20240021   copy

Prenylated and Geranylated Derivatives of Non-Oxidized Monomeric Acylphloroglucinols of Natural Origin: Occurrence, Biological Properties and Spectroscopic Data

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Phloroglucinols comprise polyphenolic compounds abundantly present in biological systems, which are synthesized and accumulated by plants, microorganisms, and marine organisms of different families. Interesting biological activities are associated with these compounds endowed with unique structural characteristics. Because of this, they have become attractive for studies in several areas, such as chemistry and pharmacology. Despite the existence of reputable reviews on phloroglucinol and its derivative compounds, updates on the subject are constant and there are still unexplored specificities of these polyphenols in the literature. Therefore, the present review compiled data on monomeric derivatives of acylphloroglucinols isolated from natural sources. These compounds were grouped into classes considering the oxidation of the central 1,3,5-trihydroxybenzene (THB) ring. Nuclear magnetic resonance (NMR) spectroscopic data and biological activities reported in the literature were associated with the cataloged metabolites considering publications from 1965 to 2022.

Keywords:
polyphenols; acylphloroglucinol; nuclear magnetic resonance; spectroscopy

1. Introduction

Phloroglucinols are polyphenolic compounds with wide occurrence in different natural sources, such as plants, microorganisms, and marine organisms. Its chemical structure is characterized by the tautomeric form 1,3,5-trihydroxybenzene (THB). However, when produced biologically, it can be converted into 1,3,5-cyclohexanetrione.11 Van Klink, J. W.; Larsen, L.; Perry, N. B.; Weavers, R. T.; Cook, G. M. Bremer, P. J.; MacKenzie, A. D.; Kirikae, T.; Bioorg. Med. Chem. 2005, 13, 6651. [Crossref]
Crossref... THB core biosynthesis occurs via the acetate-malonate pathway, starting by the conversion of acetate into acetyl coenzyme A (acetyl-CoA) catalyzed by acetyl-CoA carboxylase subunit, forming malonyl coenzyme A (malonyl-CoA) units, which are then converted into phloroglucinols via enzymatic reduction mediated by polyketide synthase.11 Van Klink, J. W.; Larsen, L.; Perry, N. B.; Weavers, R. T.; Cook, G. M. Bremer, P. J.; MacKenzie, A. D.; Kirikae, T.; Bioorg. Med. Chem. 2005, 13, 6651. [Crossref]
Crossref... ,22 Xu, X.; Xian, M.; Liu, H.; RSC Adv. 2017, 7, 50942. [Crossref]
Crossref... ,33 Schmidt, S.; Jürgenliemk, G.; Skaltsa, H.; Heilmann, J.; Phytochemistry 2012, 77, 218. [Crossref]
Crossref... ,44 Achkar, J.; Xian, M.; Zhao, H.; Frost, J. W.; J. Am. Chem. Soc. 2005, 127, 5332. [Crossref]
Crossref...

Phloroglucinol-derived molecules commonly have alkyl or acyl groups at aromatic carbon of the THB unit, allowing further cyclization and oxidation reactions. Because of this, polycyclic and caged structures can be formed.11 Van Klink, J. W.; Larsen, L.; Perry, N. B.; Weavers, R. T.; Cook, G. M. Bremer, P. J.; MacKenzie, A. D.; Kirikae, T.; Bioorg. Med. Chem. 2005, 13, 6651. [Crossref]
Crossref... ,33 Schmidt, S.; Jürgenliemk, G.; Skaltsa, H.; Heilmann, J.; Phytochemistry 2012, 77, 218. [Crossref]
Crossref... The structural variability of these derivatives provides a promising source of bioactive compounds, which can serve as a basis for the development of medicinal and supplementary healthcare products.55 Bridi, H.; Meirelles, G. C.; Poser, G. L.; Phytochemistry 2018, 155, 203. [Crossref]
Crossref... ,66 Celaj, O.; Durán, A. G.; Cennamo, P.; Scognamiglio, M.; Fiorentino, A.; Esposito, A.; D’Abrosca, B.; Phytochem. Rev. 2020, 20, 259. [Crossref]
Crossref... These compounds have been associated with biological activities, such as: antibacterial, anthelmintic, antimicrobial, antioxidant, anti-angiogenic, antibiotic, and anti-human immunodeficiency virus (HIV).11 Van Klink, J. W.; Larsen, L.; Perry, N. B.; Weavers, R. T.; Cook, G. M. Bremer, P. J.; MacKenzie, A. D.; Kirikae, T.; Bioorg. Med. Chem. 2005, 13, 6651. [Crossref]
Crossref... ,55 Bridi, H.; Meirelles, G. C.; Poser, G. L.; Phytochemistry 2018, 155, 203. [Crossref]
Crossref... ,66 Celaj, O.; Durán, A. G.; Cennamo, P.; Scognamiglio, M.; Fiorentino, A.; Esposito, A.; D’Abrosca, B.; Phytochem. Rev. 2020, 20, 259. [Crossref]
Crossref... ,77 França, H. S.; Kuster, R. M.; Rito, P. N.; de Oliveira, A. P.; Teixeira, L. A.; Rocha, L.; Quim. Nova 2009, 32, 1103. [Crossref]
Crossref... ,88 Socolsky, C.; Domínguez, L.; Asakawa, Y.; Bardón, A.; Phytochemistry 2012, 80, 115. [Crossref]
Crossref... ,99 Mathekga, A. D. M.; Meyer, J. J. M.; Horn, M. M.; Drewes, S. E.; Phytochemistry 2000, 53, 93. [Crossref]
Crossref... ,1010 Drewes, S. E.; Sandy, F. V.; Phytochemistry 2008, 69, 1745. [Crossref]
Crossref... ,1111 Rukachaisirikul, V.; Naklue, W.; Phongpaichit, S.; Towatana, N. H.; Maneenoon, K.; Tetrahedron 2006, 62, 8578. [Crossref]
Crossref... ,1212 Schempp, C. M.; Kiss, J.; Kirkin, V.; Averbeck, M.; SimonHaarhaus, B.; Kremer, B.; Termeer, C. C.; Sleeman, J.; Simon, J. C.; Planta Med. 2005, 71, 999. [Crossref]
Crossref... ,1313 Jayasuriya, H.; Clark, A. M.; McChesney, J. D.; J. Nat. Prod. 1991, 54, 1314. [Crossref]
Crossref... ,1414 Nishizawa, M.; Emura, M.; Kan, Y.; Yamada, H.; Ogawa, K.; Hamanaka, N.; Tetrahedron Lett. 1992, 33, 2983. [Crossref]
Crossref... ,1515 Grupta, P.; Kumar, R.; Garg, P.; Singh, I. P.; Bioorg. Med. Chem. Lett. 2010, 20, 4427. [Crossref]
Crossref...

The information on phloroglucinols has been reported through experimental studies and compiled in literature reviews.55 Bridi, H.; Meirelles, G. C.; Poser, G. L.; Phytochemistry 2018, 155, 203. [Crossref]
Crossref... ,66 Celaj, O.; Durán, A. G.; Cennamo, P.; Scognamiglio, M.; Fiorentino, A.; Esposito, A.; D’Abrosca, B.; Phytochem. Rev. 2020, 20, 259. [Crossref]
Crossref... ,1616 Penttilä, A.; Sundman, J.; J. Pharm. Pharmacol. 1970, 22, 393. [Crossref]
Crossref... ,1717 Singh, I. P.; Etoh, H.; Nat. Prod. Sci. 1997, 3, 1. [Link] accessed in January 2024
Link... ,1818 Tada, M.; Chiba, K.; Takakuwa, T.; Kojima, E.; J. Med. Chem. 1992, 35, 1209. [Crossref]
Crossref... ,1919 Chiba, K.; Takakuwa, T.; Tada, M.; Yoshii, T.; Biosci., Biotechnol., Biochem. 1992, 56, 1769. [Crossref]
Crossref... ,2020 Verotta, L.; Phytochem. Rev. 2002, 1, 389. [Crossref]
Crossref... ,2121 Singh, I. P.; Bharate, S. B.; Nat. Prod. Rep. 2006, 23, 558. [Crossref]
Crossref... ,2222 Singh, I. P.; Sidana, J.; Bharate, S. B.; Foley, W. J.; Nat. Prod. Rep. 2010, 27, 393. [Crossref]
Crossref... ,2323 da Silva, J. A. T.; Dobránszki, J.; Ross, S.; In Vitro Cell. Dev. Biol. 2013, 49, 1. [Crossref]
Crossref... ,2424 Singh, I. P.; Sidana, J.; Bansal, P.; Foley, W. J.; Expert Opin. Ther. Pat. 2009, 19, 847. [Crossref]
Crossref... ,2525 Yang, F.; Cao, Y.; Appl. Microbiol. Biotechnol. 2011, 93, 487. [Crossref]
Crossref... These reports consider their natural sources, such as Gutiferae, Euphorbiaceae, Aspidiaceae, Compositae, Rutaceae, Rosaceae, Clusiaceae, Lauraceae, Crassulaceae, Cannabinaceae, and Fagaceae families.2121 Singh, I. P.; Bharate, S. B.; Nat. Prod. Rep. 2006, 23, 558. [Crossref]
Crossref... However, they are especially associated with the Hypericum and Myrtaceae families.66 Celaj, O.; Durán, A. G.; Cennamo, P.; Scognamiglio, M.; Fiorentino, A.; Esposito, A.; D’Abrosca, B.; Phytochem. Rev. 2020, 20, 259. [Crossref]
Crossref... ,2121 Singh, I. P.; Bharate, S. B.; Nat. Prod. Rep. 2006, 23, 558. [Crossref]
Crossref... In addition, the occurrence of these compounds in marine organisms and microorganisms is also known.2121 Singh, I. P.; Bharate, S. B.; Nat. Prod. Rep. 2006, 23, 558. [Crossref]
Crossref...

Despite the existence of respectable reviews focusing on phloroglucinol derivatives, updates on this subject are constant and there are still unexplored specificities in the literature. Therefore, the present review has compiled data about monomeric acylphloroglucinol derivatives, prenylated and geranylated, isolated from natural sources. These compounds were grouped into classes considering the substitution pattern of the THB central ring. Nuclear magnetic resonance (NMR) spectroscopic data and the biological activities reported in the literature were associated with the cataloged metabolites considering publications from 1965 to 2022.

2. Bibliographic Sources

This review was systematically developed by compiling data from primary studies considering the period from 1965 to 2022 and considering an inclusive criterion, in which the focus is the monomeric derivatives of acylphloroglucinol. Because of this, molecules from different biosynthetic routes, such as benzophenones, were disregarded.

The selected natural metabolites were described according to the extraction, isolation, and elucidation methods. Consequently, synthetic products and phloroglucinols without the information of interest were disregarded. Molecules were grouped and described according to their structural similarities, observing chemical, biological, taxonomic, geographic, and spectroscopic data. One-dimensional NMR signals and other information were compiled without any spectroscopic correction to the primary study material; allowing to standardize and preserve original interpretations and content since the authors were not contacted.

The platforms used in the research were: Google Scholar, ACS Publications, ResearchGate, Periodicals CAPES, Science Direct, and ScienceFinder. In addition, the keywords “phloroglucinol”, “acylphloroglucinol”, “acetophenone”, “geranyl acylphloroglucinol”, and “prenyl acylphloroglucinol” were considered in the searches.

3. Biosynthetic Aspects

Plants use secondary metabolism to their own defense against biotic and abiotic factors. Further, these products are responsible for several medicinal properties of interest.2626 Erb, M.; Kliebenstein, D. J.; Plant Physiol. 2020, 184, 39. [Crossref]
Crossref... The origin of acylphloroglucinols shows that the carbonyl unit is bioenergetically favored. Phloroglucinols come from a biosynthetic route where the THB nucleus is biosynthesized by the acetate-malonate pathway, starting with the conversion of acetate into acetyl-CoA.2121 Singh, I. P.; Bharate, S. B.; Nat. Prod. Rep. 2006, 23, 558. [Crossref]
Crossref... ,2727 Nicoletti, R.; Salvatore, M.; Ferranti, P.; Andolfi, A.; Molecules 2018, 23, 3370. [Crossref]
Crossref... ,2828 Avato, P.; Stud. Nat. Prod. Chem. 2005, 30, 603. [Crossref]
Crossref...

Metabolites from different classes may have type III polyketide synthases (PKSs) as biosynthetic precursors. These enzymes, initially identified in plants, are small homodimeric proteins formed by monomers containing independent active sites, and having a catalytic triad composed by cysteine, histidine, and asparagine residues; typically, these enzymes can incorporate a specific substrate to generate a poly-β-keto intermediate, which undergoes cyclization. Subsequently, various products can be obtained through a variety of condensation reactions such as the Claisen condensation.2929 Abe, I.; J. Nat. Med. 2020, 74, 639. [Crossref]
Crossref... ,3030 Shimizu, Y.; Ogata, H.; Goto, S.; ChemBioChem 2016, 18, 50. [Crossref]
Crossref...

Furthermore, to construct a generic biosynthetic model, they relied on hyperforin through theoretical and thermodynamic insights, a polyprenylated phloroglucinol that can exist in five tautomeric forms.3131 Oziminski, W. P.; Wójtowicz, A.; Struct. Chem. 2019, 31, 657. [Crossref]
Crossref... ,3232 Bisht, R.; Bhattacharyya, A.; Shrivastava, A.; Saxena, P.; Front. Plant Sci. 2021, 12, 2155. [Crossref]
Crossref... ,3333 Ritchie, E.; Taylor, W. C.; Vautin, T. K.; Aust. J. Chem. 1965, 18, 2021. [Crossref]
Crossref... Subsequently, new studies3434 Kurosaki, F.; Mitsuma, S.; Arisawa, M.; Phytochemistry 2002, 61, 597. [Crossref]
Crossref... ,3535 Nedialkov, P. T.; Ilieva, Y.; Momekov, G.; Kokanova-Nedialkova, Z.; Fitoterapia 2018, 127, 375. [Crossref]
Crossref... suggested a direct correlation between the biosynthesis of phloroglucinol derivatives in plant species (such as those from the genera Hypericum, Acronychia, Myrtaceae) with enzymes of the type III polyketide synthase family, as also proposed to other classes of metabolites from the same bioenergetic precursors.3434 Kurosaki, F.; Mitsuma, S.; Arisawa, M.; Phytochemistry 2002, 61, 597. [Crossref]
Crossref... ,3535 Nedialkov, P. T.; Ilieva, Y.; Momekov, G.; Kokanova-Nedialkova, Z.; Fitoterapia 2018, 127, 375. [Crossref]
Crossref...

Type III PKSs catalyze a sequential decarboxylative condensation of three malonyl-CoA molecules mediated by acetyl CoA to provide a linear tetracarbonyl polyketide intermediate, which then undergoes an intramolecular Claisen type condensation with loss of both native coenzyme A and enzyme. In fact, this process is similar to the aldol reaction that occurs in the cyclization of simple phenols to obtain orselinic acid as a product. Then, formation of the acylphloroglucinol proceeds via direct enolization, as shown in Figure 1. Other reactions may occur later, from the acylphoroglucinol generated, for example: intramolecular cyclization, alkylation, acylation, alkoxylation, prenylation, and geranylation.3636 Dewick, P. M.; Medicinal Natural Products: A Biosynthetic Approach, 3rd ed.; John Wiley & Sons Ltd: Chichester, UK, 2009.,3737 Klingauf, P.; Beuerle, T.; Mellenthin, A.; El-Moghazy, S. A. M.; Boubakir, Z.; Beerhues, L.; Phytochemistry 2005, 66, 139. [Crossref]
Crossref... ,3838 Yang, X. W.; Ding, Y; Zhang, J. J.; Liu, X.; Yang, L X.; Li, X. N.; Ferreira, D.; Walker, L. A.; Xu, G.; Org. Lett. 2014, 16, 2434. [Crossref]
Crossref... ,3939 Yang, X.-W; Li, M.-M.; Liu, X.; Ferreira, D.; Ding, Y; Zhang, J. J.; Liao, Y; Qin, H. B.; Xu, G; J. Nat. Prod. 2015, 78, 885. [Crossref]
Crossref...

Figure 1
Proposed biosynthetic pathway for the formation of acylphloroglucinol core from malonyl CoA and further biotransformation’s.

It is also kwon that prenyltransferase (PT) catalyzes the addition of dimethylallyl pyrophosphate (DMAPP) to the THB core.2828 Avato, P.; Stud. Nat. Prod. Chem. 2005, 30, 603. [Crossref]
Crossref... These enzymes were detected in experiments involving culture of Hypericum calycinum cells. Furthermore, the formation of six-membered heterocyclic rings in derivatives with more than one cycle has been observed in isolated compounds of the same genus.4040 Decosterd, L. A.; Hoffmann, E.; Kyburz, R.; Bray, D.; Hostettmann, K; Planta Med. 1991, 57, 548. [Crossref]
Crossref...

4. Chemical and Biological Aspects

The systematic analysis of studies involving the structural characterization of prenylated and geranylated non-oxidized acylphloroglucinols published between 1965 and 2022 allowed the compilation of 139 substances, which are homogeneously distributed over the years (Figure 2). These compounds having unoxidized THB unities were textually described and subdivided into two subclasses already established in the literature: monocyclic and polycyclic derivatives.2121 Singh, I. P.; Bharate, S. B.; Nat. Prod. Rep. 2006, 23, 558. [Crossref]
Crossref... ,2222 Singh, I. P.; Sidana, J.; Bharate, S. B.; Foley, W. J.; Nat. Prod. Rep. 2010, 27, 393. [Crossref]
Crossref...

Figure 2
Percentage distribution over the years of natural acylphloroglucinols reported in the literature.

The metabolites were summarized in three tables over this report, and Table 1 addresses the extraction methodology and biological activities.

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Table 1
Taxonomic, extraction, and biological activity data of acylphloroglucinol derivatives

Cytotoxicity and antimicrobial actions stand out as the most frequently activities associated with the phloroglucinol derivatives reported in literature (Figure 3).

Figure 3
Biological activities associated with acylphloroglucinol derivatives.

Cytotoxic effects in phenolic derivatives behave as a cell-dependent uptake rate directly related to their lipophilicity. This activity in polyhydroxylated phenolic esters can be reduced by the presence of hydroxyl groups in the ring and by the length of the ester moiety. Consequently, the absence of these substituents is related to increased cytotoxic action.110110 Fiuza, S. M.; Gomes, C; Teixeira, L. J.; Cruz, M. T. G.; Cordeiro, M. N. D. S.; Milhazes, N.; Borges, E; Marques, M. P. M.; Bioorg. Med. Chem. 2004, 12, 3581. [Crossref]
Crossref...

The antimicrobial potential of a molecule is related to hydrophobicity issues and found to be enhanced by the increase of acyl and prenyl groups present in the side chains.111111 Karabín, M.; Hudcová, T.; Jelinek, L.; Dostálek, P.; Biotechnol. Adv. 2015, 33, 1063. [Crossref]
Crossref... ,112112 Patra, A. K. In Dietary Phytochemicals and Microbes; Patra, A. K, ed.; Springer: Dordrecht, 2012, p. 1. [Crossref]
Crossref... Monomeric acylphloroglucinols are the most related substances associated to these features. Therefore, recognizing the structural characteristics of compounds becomes important to understand the relationship between chemical structure and biological activity.

Tables 2-3 compile the data according to their nomenclature, chemical formula, taxonomic data, geographic location of specimen collection, study reference and 1H and 13C NMR data (chemical shifts, coupling constant, and the frequency and solvent used in research). As presented in Figure 4, these substances were mainly isolated from plants of the Hypericum genus.

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Table 2
Prenylated-geranylated monocyclic phloroglucinol derivatives
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Table 3
Prenylated-geranylated polycyclic phloroglucinol derivatives

Figure 4
Summary of isolated phloroglucinols distribution according to species and genera.

Considering the temporary coverage of 1965-2022, experimental studies contributed by suggesting new connections between acylphloroglucinol derivatives, taxonomic species and biological activities. In this sense, spectroscopic data allowed the identification and discovery of new secondary metabolites. Allowing the construction of the phytochemical profile of the various species of interest and enriching knowledge about the elucidation of the biosynthetic pathways of the compounds of interest.

4.1. Prenylated and geranylated monocyclic acylphloroglucinol derivatives

Monomeric acylphloroglucinol derivatives are characterized by having a THB core with a conjugated acyl substituent on the benzene ring, which are further submitted to subclassification according to the substituents. This review highlighted the existence of terpenes, glycosides, halogenates, prenylates and geranylates, cyclic polyketides, and substituted α-pyrone. To facilitate the analysis of the monomeric monocyclic acylphloroglucinols, they were numbered according to their structural similarity, referring to the pattern of hydrogenation of the “R” substituent groups attached to the THB core (Figure 5 and Table 2).

Figure 5
Standard numbering of substituents for compounds 1-88.

Compounds 1-10 are characterized by an acylated THB core with two hydroxyls and one alkoxy groups attached to the acyl group (R1) and prenyl or geranyl at R2. For the record, no biological activities were attributed to these derivatives (Figures 5-6; Tables 1-2).

Figure 6
Monocyclic monomeric derivatives of acylphloroglucinols 1-10.

Prenylated compounds 1-3 were isolated from extracts (diethyl ether/petroleum ether, 1:2) of the roots of the species Leontonyx squarrosus.4141 Bohlmann, F.; Suwita, A.; Phytochemistry 1978, 17, 1929. [Crossref]
Crossref... Associated with the genus Helichrysum, prenylated metabolites 4 and 5 were isolated from methanolic extracts of H. niveum; while geranylates 6 and 8 from root extracts in (diethyl ether/petroleum ether, 1:1) of H. gymnoconum.4242 Popoola, O. K; Marnewick, J. L.; Rautenbach, F.; Iwuoha, E. I.; Hussein, A. A.; Molecules 2015, 20, 17309. [Crossref]
Crossref... ,5858 Bohlmann, F.; Zdero, C; Phytochemistry 1979, 18, 641. [Crossref]
Crossref... Compounds 7 and 9 were obtained from the fruit extract of Evodia merrillii in 95% CH3CH2OH,and compound 10 was associated with aerial parts of Boronza ramose, extracted in sequential solvents: petroleum ether, CH3CH2OH and CH3OH.4646 Chou, C. J.; Lin, L C; Chen, K. T.; Chen, C. F; J. Nat. Prod. 1992, 55, 795. [Crossref]
Crossref... ,4848 Ahsan, M.; Gray, A. I..; Waterman; P. G; Armstrong, J. A.; J. Nat. Prod. 1994, 57, 673. [Crossref]
Crossref...

Structures 11-35 followed the pattern of alkyl groups at R1 and R3, and prenyl or geranyl groups attached to the C-5 of the THB core (Figures 5 and 7; Tables 1-2).

Figure 7
Monocyclic monomeric derivatives of acylphloroglucinols 11-35.

The prenylated derivative 11 was obtained from the extraction using ethyl acetate of the roots of Acronychia pedunculata.5050 Kumar, V.; Karunaratne, V.; Sanath, M. R.; Meegalle, K; Phytochemistry 1989, 28, 1278. [Crossref]
Crossref... Compounds 12-14 were isolated in species of the genus Helichrysum from ethanolic and methanolic extracts of roots and aerial parts of plants of the species H. gymnoconum and H. niveum; compounds 30 and 35 were also isolated from the same genus: 30 from methanolic extracts of aerial parts of H. niveum, and 35 of H. caespititium from acetonic extracts of aerial parts of the species.99 Mathekga, A. D. M.; Meyer, J. J. M.; Horn, M. M.; Drewes, S. E.; Phytochemistry 2000, 53, 93. [Crossref]
Crossref... ,1010 Drewes, S. E.; Sandy, F. V.; Phytochemistry 2008, 69, 1745. [Crossref]
Crossref... ,4242 Popoola, O. K; Marnewick, J. L.; Rautenbach, F.; Iwuoha, E. I.; Hussein, A. A.; Molecules 2015, 20, 17309. [Crossref]
Crossref... ,5858 Bohlmann, F.; Zdero, C; Phytochemistry 1979, 18, 641. [Crossref]
Crossref... The geranylated derivatives 15 and 16 were isolated from the 95% CH3CH2OH extract of Evodia merrillii fruits.4646 Chou, C. J.; Lin, L C; Chen, K. T.; Chen, C. F; J. Nat. Prod. 1992, 55, 795. [Crossref]
Crossref... ,5656 Lin, L.-C; Chou, C.-J.; Chen, K. T.; Chen, C.-F; J. Nat. Prod. 1993, 56, 926. [Crossref]
Crossref... Compound 17 was isolated from methanolic extract of the leaves of Melicope ptelefolia.5757 Shaari, K; Safri, S.; Abas, F; Lajis, N. H.; Israf, A. D.; Nat. Prod. Res. 2006, 20, 415. [Crossref]
Crossref... Geranylated molecules 18-22 and 24-29 were isolated from different species of Hypericum (H. natalitium, Hypericum spp., H. jovis, H. olympicum, and H. empetrifolium) and their structures were elucidated based on NMR spectroscopic data. Inherent to biological activities, 19 and 22 stand out. THB derivatives were isolated from extracts of aerial parts of Hypericum spp. family in an acetone/ CH3OH system, which aided in the production of biofilm by Gram-positive strains at sub-minimal inhibitory concentration (MIC) concentrations.5858 Bohlmann, F.; Zdero, C; Phytochemistry 1979, 18, 641. [Crossref]
Crossref... ,6464 Sarkisian, S. A.; Janssen, M. J.; Matta, H.; Henry, G. E.; LaPlante, K. L.; Rowley, D. C; Phytother. Res. 2011, 26, 1012. [Crossref]
Crossref... Derivative 23 was identified in a mixture of leaf extract in hexane of Esenbeckia nesiotica.6060 Rios, M. Y; Delgado, G.; Phytochemistry 1992, 31, 3491. [Crossref]
Crossref... Phloroglucinols 25-27 of the species H. olympicum were isolated from the extract of the aerial parts of the plant using the solvent gradient: hexane, CH2Cl2 and CH3OH; and exhibited potent MIC against multidrug-resistant Staphylococcus strains. In this sense, the antibacterial action of 26 stands out due to the compound containing a peroxide group in its structure, associated with high reactivity and significant instability, which can induce oxidative stress in bacteria. Compound 28 was isolated from H. jovis in cyclohexane and cited as having significant anti-inflammatory activity, with half maximal inhibitory concentration (IC50) values of 34.4.4545 Athanasas, K; Magiatis, P.; Fokialakis, N.; Skaltsounis, A. L.; Pratsinis, H.; Kletsas, D.; J. Nat. Prod. 2004, 67, 973. [Crossref]
Crossref... ,6262 Grafakou, M. E.; Barda, C; Pintać, D.; Lesjak, M.; Heilmann, J.; Skaltsa, H; Planta Med. 2021, 87, 1184. [Crossref]
Crossref... ,6969 Shiu, W. K. P.; Rahman, M. M.; Curry, J.; Stapleton, P.; Zloh, M.; Malkinson, J. P.; Gibbons, S.; J. Nat. Prod 2012, 75, 336. [Crossref]
Crossref... Further, 29 was isolated from the aerial parts, in petroleum ether, of H. empetrifolium, showing antiproliferative activity in microvascular and endothelial cells.33 Schmidt, S.; Jürgenliemk, G.; Skaltsa, H.; Heilmann, J.; Phytochemistry 2012, 77, 218. [Crossref]
Crossref...

The genus Garcinia is studied because it has several chemical constituents of pharmacological interest, including phloroglucinols. Derivatives 31-34 were related to G. dauphinensis, being isolated from ethanolic extracts of the plant’s roots and their structures elucidated by spectroscopic data. Compound 34 exhibited promising growth inhibitory activity against A2870 ovarian cancer cells, (IC50 = 4.5 ± 0.9 µM) and also showed antiplasmodial activity against the drug-resistant Dd2 strain of Plasmodium falciparum (IC50 = 0.8 ± 0.1 µM). Derivatives 31-32 were isolated from the ethanolic extract of G. dauphinensis roots, but do not show potential biological activity.6666 Fuentes, R. G.; Pearce, K. C; Du, Y; Rakotondrafara, A.; Valenciano, A. L.; Cassera, M. B.; Rasamison, V. E.; Crawford, T. D.; Kingston, D. G. L; J. Nat. Prod. 2019, 82, 431. [Crossref]
Crossref... phloroglucinols 36-50 have the THB ring functionalized by aliphatic acyl groups at C-1, hydroxyl or O-prenyl or O-geranyl at C-2, prenyl or geranyl substituents at C-3, and two hydroxyl groups at C-4 and C-5 (Figures 5 and 8; Tables 1-2).

Figure 8
Monocyclic monomeric derivatives of acylphloroglucinols 36-50.

The prenylated compound 36 was associated with the species Acronychia laurifolia, and no mention of extraction and isolation methods was provided in the report.7070 Banerji, J.; Rej, R. N.; Chatterjee, A.; Chem. Informationsdienst 1973, 4, 693. [Crossref]
Crossref... Metabolite 37 was obtained from the ethyl acetate extract of Helichrysum caespititium and showed antimicrobial activity, with significant inhibition of Staphylococcus aureus, Streptococcus pyogenes, Cryptococcus neoformans, Trichophyton rubrum, T. mentagrophytes and Microsporum canis.7171 Dekker, T. G.; Fourie, T. G; Snyckers, F. O.; Schyf, V. D.; S. Afr. J. Chem. 1983, 36, 114. [Crossref]
Crossref...

Prenylated derivatives 38 and 39 were isolated from aerial parts of H. argyrolepis (ether/petroleum ether, 1:1).7272 Bohlmann, F.; Misra, L. N.; Jakupovic, J.; Planta Med. 1984, 50, 174. [Crossref]
Crossref... Obtained from Euodia lunu-ankenda (CH2Cl2/CH3OH), compounds 40 and 43 showed antifungal activity.7373 Kumar, V.; Karunaratne, V.; Sanath, M. R.; Meegalle, K; Macleod, J. K; Phytochemistry 1990, 29, 243. [Crossref]
Crossref... The genus Melicope has a variety of interesting classes of biosynthesized compounds. In this study, compound 42 stand out with a geranylated structure and with a methoxy substituent linked to the acyl group, which was isolated from the extract of the bark of M. broadbentiana, in ether/petroleum ether/CH3OH.3232 Bisht, R.; Bhattacharyya, A.; Shrivastava, A.; Saxena, P.; Front. Plant Sci. 2021, 12, 2155. [Crossref]
Crossref... Compound 44 was associated with the aerial parts of B. ramose (extract: petroleum ether, ethyl acetate and CH3OH), without mention of biological activities.4848 Ahsan, M.; Gray, A. I..; Waterman; P. G; Armstrong, J. A.; J. Nat. Prod. 1994, 57, 673. [Crossref]
Crossref...

Derivatives 45-50 were isolated from species of the genus Hypericum and proved to be biologically relevant: 45 from H. olympicum (aerial parts in hexane/CH2Cl2/CH3OH) and exhibited minimum inhibitory concentrations (MICs) of 0.51 mg L-1 against multidrug-resistant Staphylococcus aureus strains.6969 Shiu, W. K. P.; Rahman, M. M.; Curry, J.; Stapleton, P.; Zloh, M.; Malkinson, J. P.; Gibbons, S.; J. Nat. Prod 2012, 75, 336. [Crossref]
Crossref... Compounds 46, 47 and 49 from H. faberi (methanolic extract of whole plants) exhibited cytotoxicity against the human esophageal cancer cell line (ECA-109) and against the pancreatic tumor cell line (PANC-1) in vitro.7474 Zhang, X. W.; Ye, Y. S.; Xia, F.; Yang, X W; Xu, G; Nat. Prod. Bioprospect. 2019, 9, 215. [Crossref]
Crossref... Compounds 48 and 50 were isolated from extracts in cyclohexane of aerial parts of H. jovis.6262 Grafakou, M. E.; Barda, C; Pintać, D.; Lesjak, M.; Heilmann, J.; Skaltsa, H; Planta Med. 2021, 87, 1184. [Crossref]
Crossref...

Considering compounds 51-57 (Figures 5 and 9; Tables 1-2), the prenylated derivatives 51-52, sequentially extracted in hexane/dichloromethane/CH3OH/water from A. crassipetal fruits showed activity against S. aureus (moderate in 51 and greater than the antibiotic chloramphenicol in 52).7575 Tran, T. D.; Olsson, M. A.; McMillan, D. J.; Cullen, J. K; Parsons, P. G; Reddell, P. W; Ogbourne, S. M.; Antibiotics 2020, 9, 487. [Crossref]
Crossref... Derivative 53 was isolated from M. oppositifolius leaf extracts using a mixture of CH2Cl2/CH3OH (1:1), and showed inhibitory activity against bacterial strains E. coli, S. aureus, S. typhi and P. aeruginosa with MIC ranging from 3.125 to 50 μg m L -1.7676 Tchangoue, Y. A. N.; Tchamgoue, J.; Lungae, P. K; Knepper, J.; Paltinean, R.; Ibrom, K; Crişan, G; Kouam, S. F; Ali, M. S.; Schulz, S.; Fitoterapia 2020, 42, 104527. [Crossref]
Crossref... Compounds 54 and 56 were identified in the species E. merrillii from the fruit extract in 95% CH3CH2OH.4646 Chou, C. J.; Lin, L C; Chen, K. T.; Chen, C. F; J. Nat. Prod. 1992, 55, 795. [Crossref]
Crossref... ,5656 Lin, L.-C; Chou, C.-J.; Chen, K. T.; Chen, C.-F; J. Nat. Prod. 1993, 56, 926. [Crossref]
Crossref... From H. erectum, compound 55 was isolated and found to be a potent antibacterial agent against S. aureus and B. subtilis.7777 Moon, H. L; Phytother. Res. 2010, 24, 941. [Crossref]
Crossref... ,7878 Tada, M.; Chiba, K; Yamada, H.; Maruyama, H.; Phytochemistry 1991, 30, 2559. [Crossref]
Crossref... ,7979 Lu, S.; Tanaka, N.; Tatano, Y.; Kashiwada, Y.; Fitoterapia 2016, 114, 188. [Crossref]
Crossref... Obtained from the hexane extract of the aerial parts of H. anulatum, derivative 57 was tested against tumor cells (HL-60, HL-60/DOX, MDA-MB, SKW-3, and K-562) and showed to have potent cytotoxic agent with IC50 value between 3.42-5.87 µM.3535 Nedialkov, P. T.; Ilieva, Y.; Momekov, G.; Kokanova-Nedialkova, Z.; Fitoterapia 2018, 127, 375. [Crossref]
Crossref...

Figure 9
Monocyclic monomeric derivatives of acylphloroglucinols 51-57.

Compounds 58-61 are derivatives of the genus Hypericum and characterized by having the substituent R1 as an alkyl chain, R2 varying between prenyl or geranyl, and R3 being methyl or geranyl (Figures 5 and 10; Tables 1-2).

Figure 10
Monocyclic monomeric derivatives of acylphloroglucinols 58-61.

The acylphloroglucinol 58 was obtained from petroleum ether extracts of the aerial parts of the species H. calycinum and showed antifungal and antimalarial action against C. cucumerinum and P. falciparum, respectively.4040 Decosterd, L. A.; Hoffmann, E.; Kyburz, R.; Bray, D.; Hostettmann, K; Planta Med. 1991, 57, 548. [Crossref]
Crossref... The geranylated compound 59 proved to be a potent antibacterial agent against S. aureus and B. subtilis and was obtained from the methanolic extracts of H. erectum.7979 Lu, S.; Tanaka, N.; Tatano, Y.; Kashiwada, Y.; Fitoterapia 2016, 114, 188. [Crossref]
Crossref... Compounds 60-61 were isolated by extracting the aerial parts of H. empetrifolium in petroleum ether.33 Schmidt, S.; Jürgenliemk, G.; Skaltsa, H.; Heilmann, J.; Phytochemistry 2012, 77, 218. [Crossref]
Crossref...

Regarding metabolites 62-64 (Figures 5 and 11; Tables 1-2), compound 62 was obtained from the polar fractions of a chloroform extract of the rhizome of Remirea maritima;4949 Allan, R. D.; Wells, R. J.; Macleod, J. K; Tetrahedron Lett. 1970, 11, 3945. [Crossref]
Crossref... compounds 63-64, both geranylated, were found in the species Hypericum empetrifolium and isolated from petroleum ether extracts of aerial parts.33 Schmidt, S.; Jürgenliemk, G.; Skaltsa, H.; Heilmann, J.; Phytochemistry 2012, 77, 218. [Crossref]
Crossref...

Figure 11
Monocyclic monomeric derivatives of acylphloroglucinols 62-64.

Compounds 65-77 are subdivided into the genera Hypericum and Acronychia (Figures 5 and 12; Tables 1-2): As for the first genus, prenylates 66-67 were isolated from H. laricifolium (hexane), 68 from H. foliosum (hexane), and 74 from H. empetrifolium (petroleum ether), all from aerial parts of the species.33 Schmidt, S.; Jürgenliemk, G.; Skaltsa, H.; Heilmann, J.; Phytochemistry 2012, 77, 218. [Crossref]
Crossref... ,8585 Ccana-Ccapatinta, G. V.; Poser, G. L.; Phytochem. Lett. 2015, 12, 63. [Crossref]
Crossref... ,8686 Gibbons, S.; Moser, E.; Hausmann, S.; Stavri, M.; Smith, E.; Clennett, C; Phytochem. 2005, 66, 1472. [Crossref]
Crossref... In addition, an antimicrobial action against S. aureus was associated with 68.8686 Gibbons, S.; Moser, E.; Hausmann, S.; Stavri, M.; Smith, E.; Clennett, C; Phytochem. 2005, 66, 1472. [Crossref]
Crossref... Regarding prenylated compounds of the genus Acronychia, 69-71, 73, and 75-77 were obtained from ethanolic extracts (95%) of A. oligophlebia leaves, in which 70-71, 73, and 75 were found to exhibit cytotoxic activity against MCF-7 cells with IC50 values of 56.8 (for the last three compounds).8787 Yang, X.; Zhang, Y. B.; Wu, Z. N.; Zhang, X. Q.; Jiang, J. W.; Li, Y. L.; Wang, G. C; Fitoterapia 2015, 105, 156. [Crossref]
Crossref... ,8888 Niu, Q.-W.; Chen, N.-H; Wu, Z.-N.; Luo, D.; Li, Y-Y; Zhang, Y.-B.; Li, Q.-G.; Li, Y-L; Wang, G.-C; Nat. Prod. Res. 2018, 33, 2230. [Crossref]
Crossref... Furthermore, 65 and 72 were extracted from methanolic extracts of leaves of A. pedunculata, and the latter being tested for its cytotoxic activity on deoxyribonucleic acid (DNA) polymerases and human cancer cells.5050 Kumar, V.; Karunaratne, V.; Sanath, M. R.; Meegalle, K; Phytochemistry 1989, 28, 1278. [Crossref]
Crossref... ,8383 Kozaki, S.; Takenaka, Y.; Mizushina,Y;Yamaura, T.; Tanahashi, T.; J. Nat. Med. 2014, 68, 421. [Crossref]
Crossref...

Figure 12
Monocyclic monomeric derivatives of acylphloroglucinols 65-77.

Derivatives 78-88 exhibit a wide range of variant substituents between groups such as prenyl and geranyl (Figures 5 and 13; Tables 1-2). Geranylated metabolites 78-80 were isolated from H. japonicum in different extracts: 95% ethanol (78-79, cytotoxic against HT22) and hexane (80).6868 Peng, X.; Tan, Q.; Zhou, H.; Xu, J.; Gu, Q.; Fitoterapia 2021, 153, 104984. [Crossref]
Crossref... ,8989 Hu, L. H.; Khoo, C. W; Vittal, J. J.; Sim, K. Y; Phytochemistry 2000, 53, 705. [Crossref]
Crossref... Compounds 81 (stems and roots, CH3OH), 86 (stem, bark, CH3OH), 87 (leaves, CH2Cl2), and 88 (stems and roots, CH3OH) were obtained from A. pedunculata.8282 Sy, L. K.; Brown, G. D.; Phytochemistry 1999, 52, 681. [Crossref]
Crossref... ,8484 Tanjung, M.; Nurmalasari, L; Wilujeng, A. K.; Saputri, R. D.; Rachmadiarti, F.; Tjahjandarie, T. S.; Nat. Prod. Sci. 2018, 24, 284. [Crossref]
Crossref... ,9090 Su, C.-R.; Kuo, P-C; Wang, M.-L.; Liou, M. J.; Damu, A. G.; Wu, T. S.; J. Nat. Prod. 2003, 66, 990. [Crossref]
Crossref... Compounds 82-83 were associated with ethanolic extracts from the roots of L. pulverulenta, and 84 obtained from M. barbigera leaf extracts in CH2Cl2, while 85 was isolated from L. squarrosus (aerial parts, ether/petroleum ether extract).4141 Bohlmann, F.; Suwita, A.; Phytochemistry 1978, 17, 1929. [Crossref]
Crossref... ,9191 Pascual, J. T.; Valle, M. A. M.; Gonzalez, M. S.; Bellido, I. S.; Phytochemistry 1982, 21, 791. [Crossref]
Crossref... ,9292 Le, K.-T.; Bandolik, J. J.; Kassack, M. U.; Wood, K. R.; Paetzold, C; Appelhans, M. S.; Passreiter, C. M.; Molecules 2021, 26, 688. [Crossref]
Crossref...

Figure 13
Monocyclic monomeric derivatives of acylphloroglucinols 78-88.

4.2. Bicyclic and tricyclic acylphloroglucinol derivatives

Polycyclic derivatives 89-139 were grouped according to the structural similarity of the THB core (Figures 14 and 15; Tables 1 and 3).

Figure 14
Bicyclic and tricyclic acylphloroglucinol derivatives 89-118.

Figure 15
Bicyclic and tricyclic acylphloroglucinol derivatives 119-139.

Considering the genus Helichrysum, 89, 91, and 100 were obtained from H. bellum (aerial parts in petroleum ether) and 109 from H. cerastioides (aerial parts in a 1:3 ether/petroleum ether).5858 Bohlmann, F.; Zdero, C; Phytochemistry 1979, 18, 641. [Crossref]
Crossref... ,7272 Bohlmann, F.; Misra, L. N.; Jakupovic, J.; Planta Med. 1984, 50, 174. [Crossref]
Crossref... From the genus Hypericum, 90 was isolated from aerial parts, in CH2Cl2, from H. lissophloeus, and proved to be a potent stimulator of gamma-aminobutyricacid (GABA)-induced currents in recombinant α1β2γ2; compounds 94 and 130 were isolated from H. japonicum in CH3CH2OH/H2O; a sequential extraction (CHCl3 and CH3OH) of the leaves of H. roeperianum resulted in the isolation of 95; from aerial parts of H. annulatum in hexane, 96-97 and 137 were obtained.3535 Nedialkov, P. T.; Ilieva, Y.; Momekov, G.; Kokanova-Nedialkova, Z.; Fitoterapia 2018, 127, 375. [Crossref]
Crossref... ,6565 Fobofou, S. A. T.; Franke, K; Sanna, G.; Porzel, A.; BuUita, E.; Colla, P.; Wessjohann, L. A.; Bioorg. Med. Chem. 2015, 23, 6327. [Crossref]
Crossref... ,9393 Crockett, S.; Baur, R.; Kunert, O.; Belaj, E; Sigel, E.; Bioog. Med. Chem. 2016, 24, 681. [Crossref]
Crossref... Acylphloroglucinols 98-99 and 115-116 were associated with the prospection of H. empetrifolium (aerial parts in petroleum ether), and the last two compounds showed in vitro antiproliferative activity against human microvascular endothelial cells (HMEC-1) with IC50 values from 9.2 ± 2.0 to 29.6 ± 3.5 μM.9797 Schmidt, S.; Jürgenliemk, G.; Schmidt, T. J.; Skaltsa, H.; Heilmann, J.; J. Nat. Prod. 2012, 75, 1697. [Crossref]
Crossref... Extractions using petroleum ether, diethyl ether, CH3OH and 1:1 CH3OH/water of the aerial parts from H. amblycalyx allowed the isolation of phenolic derivatives 101-104, which demonstrated antiproliferative activity against HMEC-1 with IC50 values identical to those 115-116. Further, 103 and 104 showed moderate cytotoxicity against KB (human epithelial) and Jurkat T (T lymphocyte) cancer cells.4545 Athanasas, K; Magiatis, P.; Fokialakis, N.; Skaltsounis, A. L.; Pratsinis, H.; Kletsas, D.; J. Nat. Prod. 2004, 67, 973. [Crossref]
Crossref... ,6262 Grafakou, M. E.; Barda, C; Pintać, D.; Lesjak, M.; Heilmann, J.; Skaltsa, H; Planta Med. 2021, 87, 1184. [Crossref]
Crossref... ,9797 Schmidt, S.; Jürgenliemk, G.; Schmidt, T. J.; Skaltsa, H.; Heilmann, J.; J. Nat. Prod. 2012, 75, 1697. [Crossref]
Crossref... ,9898 Winkelmann, K.; San, M.; Kypriotakis, Z.; Skaltsa, H.; Bosilij, B.; Heilmann, J.; Z. Naturforsch. C 2003, 8, 527. [Crossref]
Crossref... Compound 110 was obtained from aerial parts of H. jovis in petroleum ether.4545 Athanasas, K; Magiatis, P.; Fokialakis, N.; Skaltsounis, A. L.; Pratsinis, H.; Kletsas, D.; J. Nat. Prod. 2004, 67, 973. [Crossref]
Crossref... Compound 111 was isolated from H. prolificum (aerial parts in hexane) and was able to inhibit proliferation of MCF-7 (human breast), NCI-H460 (lung), SF-268 (CNS), AGS (stomach) and HCT-116 (colon) tumor cell lines in vitro, with IC50 values between 23 and 36 µM.101101 Henry, G. E.; Raithore, S.; Zhang, Y; Jayaprakasam, B.; Nair, M. G.; Heber, D.; Seeram, N. P.; J. Nat. Prod. 2006, 69, 1645. [Crossref]
Crossref... Exploration of the aerial parts of H. pseudopetiolatum (CH3OH) resulted in the antimicrobial 112, and from H. yojiroanum (CH3OH), compound 113.102102 Tanaka, N.; Otani, M.; Kashiwada, Y.; Takaishi, Y; Shibazaki, A.; Gonoi, T.; Shiro, M.; Kobayashi, J.; Bioorg. Med. Chem. Lett. 2010, 20, 4451. [Crossref]
Crossref... ,103103 Mamemura, T.; Tanaka, N.; Shibazaki, A.; Gonoi, T.; Kobayashi, J.; Tetrahedron Lett. 2011, 52, 3575. [Crossref]
Crossref... Metabolites 133-135 were isolated from CH3OH extracts of H. faberi along with 118 and 136 and demonstrated moderate cytotoxic (PANC-1).6767 Zhang, X. W; Fan, S. Q.; Xia, F; Ye, Y. S.; Yang, X. W;Yang, X. W; Xu, G.; J. Nat. Prod. 2019, 82, 1367. [Crossref]
Crossref...

Derivatives 92 and 127-128 have been associated with ethanolic extracts of Humulus lupulus (female inflorescences), the only species of the genus related to polycyclic phloroglucinols.9494 Li, J.; Li, N.; Li, X; Chen, G.; Wang, C; Lin, B.; Hou, Y; J. Nat. Prod. 2017, 80, 3081. [Crossref]
Crossref... Harrisonia abyssinica is another unique species of its genus correlated with this class of metabolites; however, two studies were performed, with hexanoic root extract (resulting in 93) and with CH3OH/CH2Cl2 1:1 fruit extract (resulting in 125-126); the last two compounds have antimicrobial action against C. albicans (MIC of 5 μg mL-1 for 125 and > 100 μg mL-1 for 126) and B. cereus (MIC of 6 μg mL-1 for 125 and > 100 μg mL-1 to 126).9595 Okorie, D. A.; Phytochemistry 1982, 21, 2424. [Crossref]
Crossref... ,106106 Mayaka, R. K; Langat, M. K; Omolo, J. O.; Cheplogoi, P. K; Planta Med. 2012, 78, 383. [Crossref]
Crossref... As previously described species, Bosistoa selwyn is the only one of the genera in this research and provided compound 107 from petroleum ether extracts (leaves).9999 Auzi, A. A.; Hartley, T. G; Waigh, R. D.; Waterman, P. G.; Nat. Prod. Lett. 1998, 11, 137. [Crossref]
Crossref... From the genus Garcinia, 138-139 were isolated in methanolic extracts from the roots of G. atroviridis; furthermore, 138 exhibited cytotoxicity against HeLa cells and mildly inhibitory to B. cereus and S. aureus, and 139 showed cytotoxic activity against human breast (MCF-7), human prostate (DU-145) and human lung (H-460).108108 Permana, D.; Lajis, N. H.; Mackeen, M. M.; Ali, A. M.; Aimi, N.; Kitajima, M.; Takayama, H.; J. Nat. Prod. 2001, 64, 976. [Crossref]
Crossref... ,109109 Permana, D.; Abas, E; Maulidiani; Shaari, K; Stanslas, J.; Ali, A. M.; Lajis, N. H.; Z. Naturforsch. C 2005, 60, 523. [Crossref]
Crossref...

Regarding the genus Acronychia, only two species were studied: CH3OH/CH2Cl2 (1:1) extracts of A. trifoliolata bark resulted in 121, cytotoxic molecules 105-106 (moderate antiproliferative cytotoxic activity against NCI-60), and also compound 108.5353 Miyake, K; Suzuki, A.; Morita, C; Goto, M.; Newman, D. J.; O'Keefe, B. R.; Morris-Natschke, S. L.; Lee, K H.; Goto, K. N.; J. Nat. Prod. 2016, 79, 2883. [Crossref]
Crossref... ,100100 Ito, C; Matsui, T.; Ban, Y; Wu, T. S.; Itoigawa, M.; Nat. Prod. Commun. 2016, 11, 83. [Crossref]
Crossref... Extraction of leaves and branches of A. pedunculata using CH3OH resulted in compounds 119 and 132; when extraction was performed using roots and acetone, compounds 120, 122-123 and 131 were isolated.5151 Ito, C; Hosono, M.; Tokuda, H; Wu, T. S.; Itoigawa, M.; Nat. Prod. Commun. 2016, 11, 1299. [Crossref]
Crossref... ,8383 Kozaki, S.; Takenaka, Y.; Mizushina,Y;Yamaura, T.; Tanahashi, T.; J. Nat. Med. 2014, 68, 421. [Crossref]
Crossref... Considering the genus Melicope, three specimens were isolated: 114 from methanolic extracts of leaves and branches of M. ptelefolia, 117 from leaves of M. barbigera in CH2Cl2, and 124 and 129 from CH3CH2OH extracts of the leaves of M. patulinervia.9292 Le, K.-T.; Bandolik, J. J.; Kassack, M. U.; Wood, K. R.; Paetzold, C; Appelhans, M. S.; Passreiter, C. M.; Molecules 2021, 26, 688. [Crossref]
Crossref... ,104104 Kamperdick, C; Van, N. H.; Sung, T. V; Adam, G.; Phytochemistry 1997, 45, 1049. [Crossref]
Crossref... ,105105 Vu, V-T; Nguyen, M.-T; Khoi, N.-M.; Xu, X.-J.; Kong, L.-Y; Luo, J.-G; Fitoterapia 2021, 148, 104805. [Crossref]
Crossref...

5. Spectroscopic Discussion

The compiled and standardized 13C NMR data of acylphloroglucinol derivatives are of great value for structural elucidation purposes. These spectroscopic patterns will facilitate the structural characterization of future isolated compounds and their identification in extracts or impure fractions. This is due to the presence of signals in the NMR spectra associated with similar structural fragments in multiple compounds of this class, such as the THB core and the acyl chain. On the other hand, the basic units of polycyclic acylphloroglucinols resemble benzofurans, benzopyrans and benzopyranones, but are hydroxylated. For spectroscopic data analysis, the aromatic carbon attached to the acyl group was defined as C-1 for all acylphloroglucinols compiled in this review.

5.1. Prenylated and geranylated monocyclic acylphloroglucinol derivatives

Monocyclic derivatives of acylfloroglucinol 1-88 are formed by common fragments, for example, the THB core. As a result, similar chemical environments are perceived in carbons with corresponding positions of different structures. The analysis of the 13C NMR (150 MHz, CDCl3) data for compounds 3, 18, 20, 29, 48, 50, 57, 60-61, 63-64, and 74 confirms this fact. Considering the reduced THB unit, three unprotected oxygenated carbons are observed in the aromatic ring (104.0-109.8 ppm in C-1, 95.1-106.9 ppm in C-3, and 95.1-106.3 ppm in C-5) and three non-oxygenated carbons, commonly protected by the electron density donor effect of neighboring ortho-hydroxyls (157.6-164.5 ppm in C-2, 160.1-164.5 ppm in C-4 and 159.0-164.9 ppm in C-6).

Common substituents also showed spectroscopic similarities in different structures. The acyl group can be recognized by the most unprotected sign of the carbonyl at 200.7-210.8 ppm (CDCl3 and 150 MHz), although values are seen in lower field than those observed for compounds 28, 63-64 and 78-81. The prenyl group commonly replaces the hydrogens attached to the aromatic carbons or oxygens of THB. Considering the conditions of 100 MHz and CDCl3 for compounds 65-70 and 75-76, due to the better relationship between data resolution and the number of compounds for evaluation, intervals of chemical shifts for the carbons are observed: when connected directly to the THB, signals are recorded in 121.67-123.4 ppm (mono-hydrogenated olefinic), 131.3-135.6 ppm (non-hydrogenated), 21.6-23.1 ppm (methylene), and 17.9-25.9 ppm (two methyl groups); on the other hand, compared to the previous situation, oxygen-bounded prenyl in 75-76 show significant higher chemical shift at 65.3-65.4 ppm (C-1), while other signals are seen at 118.6-118.7 ppm (C-2), 138.5-138.7 ppm (C-3), 18.1-18.2 ppm (C-4), and 25.7 ppm (C-5), which are consequence of the lower influence of oxygen atom.

Substitutions of the hydrogens at aromatic carbons in 1,3,5-trihydroxybenzene by geranyl result in patterns like those observed for the prenyl group. Because of this, the comparative relationship of the C-1 of geranyl linked to carbon and oxygen, such as for 64 and 80, respectively, is similar to the situations previously reported, including the values of chemical shifts. Although the geranyl derivatives present two isomeric forms, the E stereoisomers are more commonly found than the Z isomers, verified only in compounds 21 and 24, due to a probable energetic favoring. Furthermore, considering the analysis at CDCl3 and 150 MHz, ten carbon signals referring to this substituent were observed in metabolites 18, 20, 60-61, 63-64 and 74: 21.5-22.4 ppm (C-1), 121.4-121.9 ppm (C-2), 139.2-140.1 ppm (C-3), 39.6-39.7 ppm (C-4), 26.2-26.3 ppm (C-5), 123.5-123.6 ppm (C-6), 131.9-132.1 ppm (C-7), 25.6 ppm (C-8), 16.1-16.2 ppm (C-9) and 17.6-17.7 ppm (C-10).

5.2. Bicyclic and tricyclic acylphloroglucinol derivatives

Polycyclic compounds 89-139 have different structures, making it difficult to standardize their numbering. This diversity is due to multiple cyclization mechanisms, in which the acyl group may contributes directly (89-93, and 138-139) or indirectly (94-137) for the formation of the polycyclic ring.114 Despite this, the spectroscopic signals of the prenyl and geranyl substituents are characteristic and perceived when evaluating the NMR data. In addition, only 105 and 106 showed alkoxy groups, represented by a characteristic hydrogen singlet signal, with chemical shift values at 3.75-3.72 ppm for H-2 and H-10, respectively.

6. Conclusions

Acylphloroglucinol derivatives were compiled in this review along with their biosynthetic, taxonomic, bioactivity, structural, chemical and spectroscopic information. In nature, can generated from malonyl CoA decarboxylative condensation, and structural changes in the THB core and side chains proceed by different types of natural reactions, such as: alkylation, acylation, alkoxylation, prenylation, geranylation and cyclization. Taxonomically, they are associated with different genera and species of plants, in addition to presenting significant biological activities. Structurally, common fragments such as the THB core and substituents such as prenyl and geranyl are observed, which suggests interesting patterns for spectroscopic analysis. This information highlights the relevance of the topic of this review, which can be explored as a guide for studies involving this class of metabolites.

Acknowledgments

The authors are grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -CAPES (88887.496296/2020-00), Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (140548/2022-0), and Instituto Nacional de Ciência e Tecnologia em Biodiversidade e Produtos Naturais - INCT-BioNat (465637/2014-0), for financial support, and to Universidade Federal do Rio Grande do Norte (UFRN).

References

  • 1
    Van Klink, J. W.; Larsen, L.; Perry, N. B.; Weavers, R. T.; Cook, G. M. Bremer, P. J.; MacKenzie, A. D.; Kirikae, T.; Bioorg. Med. Chem. 2005, 13, 6651. [Crossref]
    » Crossref
  • 2
    Xu, X.; Xian, M.; Liu, H.; RSC Adv. 2017, 7, 50942. [Crossref]
    » Crossref
  • 3
    Schmidt, S.; Jürgenliemk, G.; Skaltsa, H.; Heilmann, J.; Phytochemistry 2012, 77, 218. [Crossref]
    » Crossref
  • 4
    Achkar, J.; Xian, M.; Zhao, H.; Frost, J. W.; J. Am. Chem. Soc. 2005, 127, 5332. [Crossref]
    » Crossref
  • 5
    Bridi, H.; Meirelles, G. C.; Poser, G. L.; Phytochemistry 2018, 155, 203. [Crossref]
    » Crossref
  • 6
    Celaj, O.; Durán, A. G.; Cennamo, P.; Scognamiglio, M.; Fiorentino, A.; Esposito, A.; D’Abrosca, B.; Phytochem. Rev. 2020, 20, 259. [Crossref]
    » Crossref
  • 7
    França, H. S.; Kuster, R. M.; Rito, P. N.; de Oliveira, A. P.; Teixeira, L. A.; Rocha, L.; Quim. Nova 2009, 32, 1103. [Crossref]
    » Crossref
  • 8
    Socolsky, C.; Domínguez, L.; Asakawa, Y.; Bardón, A.; Phytochemistry 2012, 80, 115. [Crossref]
    » Crossref
  • 9
    Mathekga, A. D. M.; Meyer, J. J. M.; Horn, M. M.; Drewes, S. E.; Phytochemistry 2000, 53, 93. [Crossref]
    » Crossref
  • 10
    Drewes, S. E.; Sandy, F. V.; Phytochemistry 2008, 69, 1745. [Crossref]
    » Crossref
  • 11
    Rukachaisirikul, V.; Naklue, W.; Phongpaichit, S.; Towatana, N. H.; Maneenoon, K.; Tetrahedron 2006, 62, 8578. [Crossref]
    » Crossref
  • 12
    Schempp, C. M.; Kiss, J.; Kirkin, V.; Averbeck, M.; SimonHaarhaus, B.; Kremer, B.; Termeer, C. C.; Sleeman, J.; Simon, J. C.; Planta Med. 2005, 71, 999. [Crossref]
    » Crossref
  • 13
    Jayasuriya, H.; Clark, A. M.; McChesney, J. D.; J. Nat. Prod. 1991, 54, 1314. [Crossref]
    » Crossref
  • 14
    Nishizawa, M.; Emura, M.; Kan, Y.; Yamada, H.; Ogawa, K.; Hamanaka, N.; Tetrahedron Lett. 1992, 33, 2983. [Crossref]
    » Crossref
  • 15
    Grupta, P.; Kumar, R.; Garg, P.; Singh, I. P.; Bioorg. Med. Chem. Lett. 2010, 20, 4427. [Crossref]
    » Crossref
  • 16
    Penttilä, A.; Sundman, J.; J. Pharm. Pharmacol. 1970, 22, 393. [Crossref]
    » Crossref
  • 17
    Singh, I. P.; Etoh, H.; Nat. Prod. Sci. 1997, 3, 1. [Link] accessed in January 2024
    » Link
  • 18
    Tada, M.; Chiba, K.; Takakuwa, T.; Kojima, E.; J. Med. Chem. 1992, 35, 1209. [Crossref]
    » Crossref
  • 19
    Chiba, K.; Takakuwa, T.; Tada, M.; Yoshii, T.; Biosci., Biotechnol., Biochem. 1992, 56, 1769. [Crossref]
    » Crossref
  • 20
    Verotta, L.; Phytochem. Rev. 2002, 1, 389. [Crossref]
    » Crossref
  • 21
    Singh, I. P.; Bharate, S. B.; Nat. Prod. Rep. 2006, 23, 558. [Crossref]
    » Crossref
  • 22
    Singh, I. P.; Sidana, J.; Bharate, S. B.; Foley, W. J.; Nat. Prod. Rep. 2010, 27, 393. [Crossref]
    » Crossref
  • 23
    da Silva, J. A. T.; Dobránszki, J.; Ross, S.; In Vitro Cell. Dev. Biol. 2013, 49, 1. [Crossref]
    » Crossref
  • 24
    Singh, I. P.; Sidana, J.; Bansal, P.; Foley, W. J.; Expert Opin. Ther. Pat. 2009, 19, 847. [Crossref]
    » Crossref
  • 25
    Yang, F.; Cao, Y.; Appl. Microbiol. Biotechnol. 2011, 93, 487. [Crossref]
    » Crossref
  • 26
    Erb, M.; Kliebenstein, D. J.; Plant Physiol. 2020, 184, 39. [Crossref]
    » Crossref
  • 27
    Nicoletti, R.; Salvatore, M.; Ferranti, P.; Andolfi, A.; Molecules 2018, 23, 3370. [Crossref]
    » Crossref
  • 28
    Avato, P.; Stud. Nat. Prod. Chem. 2005, 30, 603. [Crossref]
    » Crossref
  • 29
    Abe, I.; J. Nat. Med. 2020, 74, 639. [Crossref]
    » Crossref
  • 30
    Shimizu, Y.; Ogata, H.; Goto, S.; ChemBioChem 2016, 18, 50. [Crossref]
    » Crossref
  • 31
    Oziminski, W. P.; Wójtowicz, A.; Struct. Chem. 2019, 31, 657. [Crossref]
    » Crossref
  • 32
    Bisht, R.; Bhattacharyya, A.; Shrivastava, A.; Saxena, P.; Front. Plant Sci. 2021, 12, 2155. [Crossref]
    » Crossref
  • 33
    Ritchie, E.; Taylor, W. C.; Vautin, T. K.; Aust. J. Chem. 1965, 18, 2021. [Crossref]
    » Crossref
  • 34
    Kurosaki, F.; Mitsuma, S.; Arisawa, M.; Phytochemistry 2002, 61, 597. [Crossref]
    » Crossref
  • 35
    Nedialkov, P. T.; Ilieva, Y.; Momekov, G.; Kokanova-Nedialkova, Z.; Fitoterapia 2018, 127, 375. [Crossref]
    » Crossref
  • 36
    Dewick, P. M.; Medicinal Natural Products: A Biosynthetic Approach, 3rd ed.; John Wiley & Sons Ltd: Chichester, UK, 2009.
  • 37
    Klingauf, P.; Beuerle, T.; Mellenthin, A.; El-Moghazy, S. A. M.; Boubakir, Z.; Beerhues, L.; Phytochemistry 2005, 66, 139. [Crossref]
    » Crossref
  • 38
    Yang, X. W.; Ding, Y; Zhang, J. J.; Liu, X.; Yang, L X.; Li, X. N.; Ferreira, D.; Walker, L. A.; Xu, G.; Org. Lett. 2014, 16, 2434. [Crossref]
    » Crossref
  • 39
    Yang, X.-W; Li, M.-M.; Liu, X.; Ferreira, D.; Ding, Y; Zhang, J. J.; Liao, Y; Qin, H. B.; Xu, G; J. Nat. Prod. 2015, 78, 885. [Crossref]
    » Crossref
  • 40
    Decosterd, L. A.; Hoffmann, E.; Kyburz, R.; Bray, D.; Hostettmann, K; Planta Med. 1991, 57, 548. [Crossref]
    » Crossref
  • 41
    Bohlmann, F.; Suwita, A.; Phytochemistry 1978, 17, 1929. [Crossref]
    » Crossref
  • 42
    Popoola, O. K; Marnewick, J. L.; Rautenbach, F.; Iwuoha, E. I.; Hussein, A. A.; Molecules 2015, 20, 17309. [Crossref]
    » Crossref
  • 43
    Bohlmann, F.; Mahanta, P. K; Phytochemistry 1979, 18, 348. [Crossref]
    » Crossref
  • 44
    Henry, G E.; Campbell, M. S.; Zelinsky, A. A.; Liu, Y; Bowen-Forbes, C. S.; Li, L.; Nair, M. G.; Rowley, D. C; Seeram, N. P.; Phytother. Res. 2009, 23, 1759. [Crossref]
    » Crossref
  • 45
    Athanasas, K; Magiatis, P.; Fokialakis, N.; Skaltsounis, A. L.; Pratsinis, H.; Kletsas, D.; J. Nat. Prod. 2004, 67, 973. [Crossref]
    » Crossref
  • 46
    Chou, C. J.; Lin, L C; Chen, K. T.; Chen, C. F; J. Nat. Prod. 1992, 55, 795. [Crossref]
    » Crossref
  • 47
    Adsersen, A.; Smitt, U. W; Simonsen, H. T.; Christensen, S. B.; Jaroszewski, J. W.; Biochem. Syst. Ecol. 2007, 35, 447. [Crossref]
    » Crossref
  • 48
    Ahsan, M.; Gray, A. I..; Waterman; P. G; Armstrong, J. A.; J. Nat. Prod. 1994, 57, 673. [Crossref]
    » Crossref
  • 49
    Allan, R. D.; Wells, R. J.; Macleod, J. K; Tetrahedron Lett. 1970, 11, 3945. [Crossref]
    » Crossref
  • 50
    Kumar, V.; Karunaratne, V.; Sanath, M. R.; Meegalle, K; Phytochemistry 1989, 28, 1278. [Crossref]
    » Crossref
  • 51
    Ito, C; Hosono, M.; Tokuda, H; Wu, T. S.; Itoigawa, M.; Nat. Prod. Commun. 2016, 11, 1299. [Crossref]
    » Crossref
  • 52
    Parsons, I. C; Gray, A. I.; Hartley, T. G; Waterman, P. G.; Phytochemistry 1994, 37, 565. [Crossref]
    » Crossref
  • 53
    Miyake, K; Suzuki, A.; Morita, C; Goto, M.; Newman, D. J.; O'Keefe, B. R.; Morris-Natschke, S. L.; Lee, K H.; Goto, K. N.; J. Nat. Prod. 2016, 79, 2883. [Crossref]
    » Crossref
  • 54
    Robertson, L. P.; Lucantoni, L.; Duffy, S.; Avery, V. M.; Carroll, A. R.; J. Nat. Prod. 2019, 82, 1019. [Crossref]
    » Crossref
  • 55
    Bremner, P. D.; Meyer, J. J. M.; S. Afr. J. Bot. 2000, 66, 115. [Crossref]
    » Crossref
  • 56
    Lin, L.-C; Chou, C.-J.; Chen, K. T.; Chen, C.-F; J. Nat. Prod. 1993, 56, 926. [Crossref]
    » Crossref
  • 57
    Shaari, K; Safri, S.; Abas, F; Lajis, N. H.; Israf, A. D.; Nat. Prod. Res. 2006, 20, 415. [Crossref]
    » Crossref
  • 58
    Bohlmann, F.; Zdero, C; Phytochemistry 1979, 18, 641. [Crossref]
    » Crossref
  • 59
    Bohlmann, F.; Abraham, W. R.; Robinson, H; King, R. M.; Phytochemistry 1980, 19, 2475. [Crossref]
    » Crossref
  • 60
    Rios, M. Y; Delgado, G.; Phytochemistry 1992, 31, 3491. [Crossref]
    » Crossref
  • 61
    Gamiotea-Turro, D.; Cuesta-Rubio, O.; Prieto-González, S.; de Simone, F; Passi, S.; Rastrelli, L.; J. Nat. Prod. 2004, 67, 869. [Crossref]
    » Crossref
  • 62
    Grafakou, M. E.; Barda, C; Pintać, D.; Lesjak, M.; Heilmann, J.; Skaltsa, H; Planta Med. 2021, 87, 1184. [Crossref]
    » Crossref
  • 63
    Crockett, S. L.; Wenzig, E. M.; Kunert, O.; Bauer, R.; Phytochem. Lett. 2008, 1, 37. [Crossref]
    » Crossref
  • 64
    Sarkisian, S. A.; Janssen, M. J.; Matta, H.; Henry, G. E.; LaPlante, K. L.; Rowley, D. C; Phytother. Res. 2011, 26, 1012. [Crossref]
    » Crossref
  • 65
    Fobofou, S. A. T.; Franke, K; Sanna, G.; Porzel, A.; BuUita, E.; Colla, P.; Wessjohann, L. A.; Bioorg. Med. Chem. 2015, 23, 6327. [Crossref]
    » Crossref
  • 66
    Fuentes, R. G.; Pearce, K. C; Du, Y; Rakotondrafara, A.; Valenciano, A. L.; Cassera, M. B.; Rasamison, V. E.; Crawford, T. D.; Kingston, D. G. L; J. Nat. Prod. 2019, 82, 431. [Crossref]
    » Crossref
  • 67
    Zhang, X. W; Fan, S. Q.; Xia, F; Ye, Y. S.; Yang, X. W;Yang, X. W; Xu, G.; J. Nat. Prod. 2019, 82, 1367. [Crossref]
    » Crossref
  • 68
    Peng, X.; Tan, Q.; Zhou, H.; Xu, J.; Gu, Q.; Fitoterapia 2021, 153, 104984. [Crossref]
    » Crossref
  • 69
    Shiu, W. K. P.; Rahman, M. M.; Curry, J.; Stapleton, P.; Zloh, M.; Malkinson, J. P.; Gibbons, S.; J. Nat. Prod 2012, 75, 336. [Crossref]
    » Crossref
  • 70
    Banerji, J.; Rej, R. N.; Chatterjee, A.; Chem. Informationsdienst 1973, 4, 693. [Crossref]
    » Crossref
  • 71
    Dekker, T. G.; Fourie, T. G; Snyckers, F. O.; Schyf, V. D.; S. Afr. J. Chem. 1983, 36, 114. [Crossref]
    » Crossref
  • 72
    Bohlmann, F.; Misra, L. N.; Jakupovic, J.; Planta Med. 1984, 50, 174. [Crossref]
    » Crossref
  • 73
    Kumar, V.; Karunaratne, V.; Sanath, M. R.; Meegalle, K; Macleod, J. K; Phytochemistry 1990, 29, 243. [Crossref]
    » Crossref
  • 74
    Zhang, X. W.; Ye, Y. S.; Xia, F.; Yang, X W; Xu, G; Nat. Prod. Bioprospect. 2019, 9, 215. [Crossref]
    » Crossref
  • 75
    Tran, T. D.; Olsson, M. A.; McMillan, D. J.; Cullen, J. K; Parsons, P. G; Reddell, P. W; Ogbourne, S. M.; Antibiotics 2020, 9, 487. [Crossref]
    » Crossref
  • 76
    Tchangoue, Y. A. N.; Tchamgoue, J.; Lungae, P. K; Knepper, J.; Paltinean, R.; Ibrom, K; Crişan, G; Kouam, S. F; Ali, M. S.; Schulz, S.; Fitoterapia 2020, 42, 104527. [Crossref]
    » Crossref
  • 77
    Moon, H. L; Phytother. Res. 2010, 24, 941. [Crossref]
    » Crossref
  • 78
    Tada, M.; Chiba, K; Yamada, H.; Maruyama, H.; Phytochemistry 1991, 30, 2559. [Crossref]
    » Crossref
  • 79
    Lu, S.; Tanaka, N.; Tatano, Y.; Kashiwada, Y.; Fitoterapia 2016, 114, 188. [Crossref]
    » Crossref
  • 80
    Han, X.; Pathmasiri, W.; Bohlin, L.; Janson, J. C.; J. Chromatogr. A 2004, 1022, 213. [Crossref]
    » Crossref
  • 81
    Pathmasiri, W.; El-Seedi, H. R.; Han, X.; Janson, J. C; Huss, U.; Bohlin, L.; Chem. Biodiversity 2005, 2, 463. [Crossref]
    » Crossref
  • 82
    Sy, L. K.; Brown, G. D.; Phytochemistry 1999, 52, 681. [Crossref]
    » Crossref
  • 83
    Kozaki, S.; Takenaka, Y.; Mizushina,Y;Yamaura, T.; Tanahashi, T.; J. Nat. Med. 2014, 68, 421. [Crossref]
    » Crossref
  • 84
    Tanjung, M.; Nurmalasari, L; Wilujeng, A. K.; Saputri, R. D.; Rachmadiarti, F.; Tjahjandarie, T. S.; Nat. Prod. Sci. 2018, 24, 284. [Crossref]
    » Crossref
  • 85
    Ccana-Ccapatinta, G. V.; Poser, G. L.; Phytochem. Lett. 2015, 12, 63. [Crossref]
    » Crossref
  • 86
    Gibbons, S.; Moser, E.; Hausmann, S.; Stavri, M.; Smith, E.; Clennett, C; Phytochem. 2005, 66, 1472. [Crossref]
    » Crossref
  • 87
    Yang, X.; Zhang, Y. B.; Wu, Z. N.; Zhang, X. Q.; Jiang, J. W.; Li, Y. L.; Wang, G. C; Fitoterapia 2015, 105, 156. [Crossref]
    » Crossref
  • 88
    Niu, Q.-W.; Chen, N.-H; Wu, Z.-N.; Luo, D.; Li, Y-Y; Zhang, Y.-B.; Li, Q.-G.; Li, Y-L; Wang, G.-C; Nat. Prod. Res. 2018, 33, 2230. [Crossref]
    » Crossref
  • 89
    Hu, L. H.; Khoo, C. W; Vittal, J. J.; Sim, K. Y; Phytochemistry 2000, 53, 705. [Crossref]
    » Crossref
  • 90
    Su, C.-R.; Kuo, P-C; Wang, M.-L.; Liou, M. J.; Damu, A. G.; Wu, T. S.; J. Nat. Prod. 2003, 66, 990. [Crossref]
    » Crossref
  • 91
    Pascual, J. T.; Valle, M. A. M.; Gonzalez, M. S.; Bellido, I. S.; Phytochemistry 1982, 21, 791. [Crossref]
    » Crossref
  • 92
    Le, K.-T.; Bandolik, J. J.; Kassack, M. U.; Wood, K. R.; Paetzold, C; Appelhans, M. S.; Passreiter, C. M.; Molecules 2021, 26, 688. [Crossref]
    » Crossref
  • 93
    Crockett, S.; Baur, R.; Kunert, O.; Belaj, E; Sigel, E.; Bioog. Med. Chem. 2016, 24, 681. [Crossref]
    » Crossref
  • 94
    Li, J.; Li, N.; Li, X; Chen, G.; Wang, C; Lin, B.; Hou, Y; J. Nat. Prod. 2017, 80, 3081. [Crossref]
    » Crossref
  • 95
    Okorie, D. A.; Phytochemistry 1982, 21, 2424. [Crossref]
    » Crossref
  • 96
    Hu, L; Liu, Y; Wang, Y; Wang, Z; Huang, J.; Xue, Y; Liu, J.; Liu, Z.; Chen, Y; Zhang, Y; RSC Adv. 2018, 8, 24101. [Crossref]
    » Crossref
  • 97
    Schmidt, S.; Jürgenliemk, G.; Schmidt, T. J.; Skaltsa, H.; Heilmann, J.; J. Nat. Prod. 2012, 75, 1697. [Crossref]
    » Crossref
  • 98
    Winkelmann, K.; San, M.; Kypriotakis, Z.; Skaltsa, H.; Bosilij, B.; Heilmann, J.; Z. Naturforsch. C 2003, 8, 527. [Crossref]
    » Crossref
  • 99
    Auzi, A. A.; Hartley, T. G; Waigh, R. D.; Waterman, P. G.; Nat. Prod. Lett. 1998, 11, 137. [Crossref]
    » Crossref
  • 100
    Ito, C; Matsui, T.; Ban, Y; Wu, T. S.; Itoigawa, M.; Nat. Prod. Commun. 2016, 11, 83. [Crossref]
    » Crossref
  • 101
    Henry, G. E.; Raithore, S.; Zhang, Y; Jayaprakasam, B.; Nair, M. G.; Heber, D.; Seeram, N. P.; J. Nat. Prod. 2006, 69, 1645. [Crossref]
    » Crossref
  • 102
    Tanaka, N.; Otani, M.; Kashiwada, Y.; Takaishi, Y; Shibazaki, A.; Gonoi, T.; Shiro, M.; Kobayashi, J.; Bioorg. Med. Chem. Lett. 2010, 20, 4451. [Crossref]
    » Crossref
  • 103
    Mamemura, T.; Tanaka, N.; Shibazaki, A.; Gonoi, T.; Kobayashi, J.; Tetrahedron Lett. 2011, 52, 3575. [Crossref]
    » Crossref
  • 104
    Kamperdick, C; Van, N. H.; Sung, T. V; Adam, G.; Phytochemistry 1997, 45, 1049. [Crossref]
    » Crossref
  • 105
    Vu, V-T; Nguyen, M.-T; Khoi, N.-M.; Xu, X.-J.; Kong, L.-Y; Luo, J.-G; Fitoterapia 2021, 148, 104805. [Crossref]
    » Crossref
  • 106
    Mayaka, R. K; Langat, M. K; Omolo, J. O.; Cheplogoi, P. K; Planta Med. 2012, 78, 383. [Crossref]
    » Crossref
  • 107
    Akazawa, H.; Kohno, H.; Tokuda, H.; Suzuki, N.; Yasukawa, K; Kimura, Y; Manosroi, A.; Manosroi, J.; Akihisa, T.; Chem. Biodiversity 2012, 9, 1045. [Crossref]
    » Crossref
  • 108
    Permana, D.; Lajis, N. H.; Mackeen, M. M.; Ali, A. M.; Aimi, N.; Kitajima, M.; Takayama, H.; J. Nat. Prod. 2001, 64, 976. [Crossref]
    » Crossref
  • 109
    Permana, D.; Abas, E; Maulidiani; Shaari, K; Stanslas, J.; Ali, A. M.; Lajis, N. H.; Z. Naturforsch. C 2005, 60, 523. [Crossref]
    » Crossref
  • 110
    Fiuza, S. M.; Gomes, C; Teixeira, L. J.; Cruz, M. T. G.; Cordeiro, M. N. D. S.; Milhazes, N.; Borges, E; Marques, M. P. M.; Bioorg. Med. Chem. 2004, 12, 3581. [Crossref]
    » Crossref
  • 111
    Karabín, M.; Hudcová, T.; Jelinek, L.; Dostálek, P.; Biotechnol. Adv. 2015, 33, 1063. [Crossref]
    » Crossref
  • 112
    Patra, A. K. In Dietary Phytochemicals and Microbes; Patra, A. K, ed.; Springer: Dordrecht, 2012, p. 1. [Crossref]
    » Crossref
  • 113
    Phang, Y. L.; Liu, S.; Zheng, C.; Xu, H.; Nat. Prod. Rep. 2022, 39, 1766. [Crossref]
    » Crossref

Edited by

Editor handled this article: Paulo Cezar Vieira

Publication Dates

  • Publication in this collection
    26 Feb 2024
  • Date of issue
    2024

History

  • Received
    06 July 2023
  • Accepted
    15 Feb 2024
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