C<sub>15</sub> acetogenins from the <i>Laurencia</i> complex: 50 years of research – an overview

Wanke, Tauana; Philippus, Ana Cláudia; Zatelli, Gabriele Andressa; Vieira, Lucas Felipe Oliveira; Lhullier, Cintia; Falkenberg, Miriam

doi:10.1016/j.bjp.2015.07.027

Tauana Wanke

Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

Ana Cláudia Philippus

Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

Gabriele Andressa Zatelli

Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

Lucas Felipe Oliveira Vieira

Curso de Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

Cintia Lhullier

Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

Miriam Falkenberg ^** Corresponding author. E-mail:miriam.falkenberg@ufsc.br (M. Falkenberg).

Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

* Corresponding author. E-mail:miriam.falkenberg@ufsc.br (M. Falkenberg).

Conflicts of interest

The authors declare no conflicts of interest.

Authors’ contributions

All authors contributed in collecting and analyzing data besides drafting parts of the paper. TW (PhD student), ACP (Master student), GAZ (MSc), LFOV (Undergraduate student) and CL (postdoc fellowship) contributed also drawing the structures. MF (Professor) organized the data and contributed to critical reading of the manuscript. All the authors have read the final manuscript and approved the submission.

Species	Compounds	Biological activities
Chondrophycus glandulifer = L. glandulifera	133-36	Prolongs sleep-time by pentobarbitone (Kaul et al., 2011Kaul, N.P., Kulkarni, S.K., Kurosawa, E., 2011. Novel substances of marine origin as drug metabolism inhibitors. J. Pharm. Pharmacol. 30, 589-590.)
Chondrophycus glandulifer = L. glandulifera	133-36	Antistaphylococca l (MRSA) (Kladi et el., 2008Kladi, M., Vagias, C., Stavri, M., Rahman, M.M., Gibbons, S., Roussis, V., 2008. C15 acetogenins with antistaphyloccocal activity from the ref alga Laurencia glandulifera. Phytochem. Lett. 1, 31-36.)
L. ela ta	55, also isolated from L. pannosa	Anti bacterial activity against C. violaceum (Suzuki et al., 2001Suzuki, M., Daitoh, M., Vairappan, C.S., Abe, T., Masuda, M., 2001. Novel halogenated metabolites from the Malaysian Laurencia pannosa. J. Nat. Prod. 64, 597-602.) but no appreciable antitumour activity (Dias et al., 2011Dias, D.A., Urban, S., 2011. Phytochemical studies of the southern Australian marine alga, Laurencia elata. Phytochemistry 72, 2081-2089.)
L.obtusa	100	Antibacterial activity against Bacillus subtilisand E. coli (Caccamese et al., 1980Caccamese, S., Azzolina, R., Duesler, E.N., Paul, I.C., Rinehart Jr., K.L., 1980. Laurencienyne, a new acetylenic cyclic ether from the marine red alga Laurencia obtusa. Tetrahedron Lett. 21, 2299–2302.)
L.obtusa	114 and 115	Apoptosis inhibition of blood neutrophils (Ayyad et al., 2011Ayyad, S.E.N., Al-Footy, K.O., Alarif, W.M., Sobahi, T.R., Bassaif, S.A., Makki, M.S., Asiri, A.M., Al Halwani, A.Y., Badria, A.F., Badria, F.A., 2011. Bioactive C15 acetogenins from the red alga Laurencia obtusa. Chem. Pharm. Bull. 59, 1294-1298.)
L. nipponica	2 and 3	Insecticidal against mosquito larvae (Watanabe et al., 1989Watanabe, K., Umeda, K., Miyakado, M., 1989. Isolation and identification of three insecticidal principles from the red alga Laurencia nipponica Yamada. Agric. Biol. Chem. 53, 2513-2515.)
	3 and 4	Prolongs sleep-time by pentobarbi ton e (Kaul et al., 2011Kaul, N.P., Kulkarni, S.K., Kurosawa, E., 2011. Novel substances of marine origin as drug metabolism inhibitors. J. Pharm. Pharmacol. 30, 589-590.)
Laurencia sp	168	Antibacterial activi ty against C. violaceum, Clostridium cellobioparum and Vibrio parahaemolyticus (Vairappan et al., 2001aVairappan, C.S., Daitoh, M., Suzuki, M., Abe, T., Masuda, M., 2001. Antibacterial halogenated metabolites from the Malaysian Laurencia species. Phytochemistry 58, 291-297.).
Laurencia sp	163 and 166	Cytotoxic against solid tumours and leukaemia L1210 cells (Abdel-Mageed et al., 2010Abdel-Mageed, W.M., Ebel, R., Valeriote, F.A., Jaspars, M., 2010. Laurefurenynes A–F, new cyclic ether acetogenins from a marine red alga, Laurencia sp.. Tetrahedron 66, 2855-2862.)
Osmundea pinnatifida = L. pinnatifida	56	Antibacterial activity against food pathogens (Kinnel et al., 1979Kinnel, R.B., Dieter, R.K., Meinwald, J., Van Engen, D., Clardy, J., Eisner, T., Stallard, M.O., Fenical, W., 1979. Brasilenyne and cis-dihydrorhodophytin: antifeedant medium-ring haloethers from a sea hare (Aplysia brasiliana). Proc. Natl. Acad. Sci. U. S. A. 76, 3576-3579.); antifeedant activity (Vairappan and Tan, 2009Vairappan, C.S., Tan, K.L., 2009. C15 halogenated acetogenin with antibacterial activity against food pathogens. Malays. J. Sci. 28, 263-268.)

Species of Aplysia	Compounds	Biological activities
A. dactylomela	174 also isolated from Laurencia (Suzuki et al., 1999Suzuki, M., Nakano, S., Takahashi, Y., Abe, T., Masuda, M., 1999. Bisezakyne-A and -B, halogenated C15 acetogenins from a Japanese Laurencia species. Phytochemistry 51, 657-662.)	Activity in increasing blood levels of pentobarbital in a dose-dependent (Kaul and Kulkarni, 1978Kaul, N.P., Kulkarni, S.K., 1978. New drug metabolism inhibitor of marine origin. J. Pharm. Sci. 67, 1293-1296.)
A. dactylomela	178and 45	Antifeedant against Carassius auratus (Manzo et al., 2005Manzo, E., Ciavatta, M.L., Gavagnin, M., Puliti, R., Mollo, E., Guo, Y.W., Mattia, C.A., Mazzarella, L., Cimino, G., 2005. Structure and absolute stereochemistry of novel C15-halogenated acetogenins from the anaspidean mollusc Aplysia dactylomela. Tetrahedron 61, 7456-7460.); toxicity to brine shrimp but inactive against marine bacteria (Takahashi et al., 2002Takahashi, Y., Daitoh, M., Suzuki, M., Abe, T., Masuda, M., 2002. Halogenated metabolites from the new Okinawan red alga Laurencia yonaguniensis. J. Nat. Prod. 65, 395-398.)
A. dactylomela	167 and 179, also isolated from Laurencia sp(Vairappan et al., 2001Vairappan, C.S., Daitoh, M., Suzuki, M., Abe, T., Masuda, M., 2001. Antibacterial halogenated metabolites from the Malaysian Laurencia species. Phytochemistry 58, 291-297.)	Antibacterial activity against marine bacteria (Vairappan et al, 2001aVairappan, C.S., Daitoh, M., Suzuki, M., Abe, T., Masuda, M., 2001. Antibacterial halogenated metabolites from the Malaysian Laurencia species. Phytochemistry 58, 291-297.,bVairappan, C.S., Suzuki, M., Abe, T., Masuda, M., 2001. Halogenated metabolites with antibacterial activity from the Okinawan Laurencia species. Phytochemistry 58, 517-523.)
A. fasciata = A. brasiliana	56, also isolated from Laurencia sp (Brennan and Erickson, 1982Brennan, M.R., Erickson, K.L., 1982. Austradiol acetate and austradiol diacetate, 4,6-dihydroxy-(+)-selinane derivatives from an Australian Laurencia sp.. J. Org. Chem. 47, 3917-3921.; Norte et al., 1989Norte, M., Fernández, J.J., Cataldo, F., González, G., 1989a. E-dihydrorhodophytin, a C15 acetogenin from the red alga Laurencia pinnatifida. Phytochemistry 28, 647-649.; Vairappan and Tan, 2009Waraszkiewicz, S.M., Sun, H.H., Erickson, K.L., 1976. C15 halogenated compounds from the Hawaiian marine alga Laurencia nidifica. Maneonenes. Tetrahedron Lett. 17, 3021-3024.)	Antifeedant again st Xiphophorus helleri (Kinnel et al., 1977Kinnel, R.B., Duggan, A.J., Eisner, T., Meinwald, J., 1977. Panacene: an aromatic bromoallene from a sea hare (Aplysia brasiliana). Tetrahedron Lett. 18, 3913-3916.); ant ibacte rial activity against Salmonella enteritidis, Vibrio cholerae, Staphylococcus aureus,E. coli, S. typhi and S. thyphimurium (Vairapp an and Tan, 2009Waraszkiewicz, S.M., Sun, H.H., Erickson, K.L., 1976. C15 halogenated compounds from the Hawaiian marine alga Laurencia nidifica. Maneonenes. Tetrahedron Lett. 17, 3021-3024.)
A. fasciata= A. brasiliana	184	Antifeedant activity (Kinnel et al., 1979Kinnel, R.B., Dieter, R.K., Meinwald, J., Van Engen, D., Clardy, J., Eisner, T., Stallard, M.O., Fenical, W., 1979. Brasilenyne and cis-dihydrorhodophytin: antifeedant medium-ring haloethers from a sea hare (Aplysia brasiliana). Proc. Natl. Acad. Sci. U. S. A. 76, 3576-3579.)
A. kurodai	190	Inhibitor Na, K-ATPase (Okamoto et al., 2001Okamoto, Y., Nitanda, N., Ojika, M., Sakagami, Y., 2001. Aplysiallene, a new bromoallene as an Na, K-ATPase inhibitor from the sea hare, Aplysia kurodai. Biosci. Biotechnol. Biochem. 65, 474-476.)
A. parvula	189	Icht hyotoxic activi ty (Myiamoto et al., 1995Myiamoto, T., Ebisawa, Y., Higuchi, R., 1995. Aplyparvunin, a bioactive acetogenin from the sea hare Aplysia parvula. Tetrahedron Lett. 36, 6073-6074.)

[1] * Corresponding author. E-mail:miriam.falkenberg@ufsc.br (M. Falkenberg).

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C₁₅ acetogenins from the Laurencia complex: 50 years of research – an overview

Abstract

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Brasil

C15 acetogenins from the Laurencia complex: 50 years of research – an overview

Abstract

C₁₅ acetogenins from the Laurencia complex: 50 years of research – an overview