Screening of Brazilian plants for antimicrobial and dnadamaging activities: I. Atlantic rain forest . Ecological station juréia-itatins

Triagem de plantas nativas do Brasil para atividades antimicrobiana e de Danos no DNA: I. Mata Atlântica – Estação Ecológica Juréia-Itatins

Screening of Brazilian plants for antimicrobial and dnadamaging activities. I. Atlantic rain forest . Ecological station juréia-itatins

Triagem de plantas nativas do Brasil para atividades antimicrobiana e de Danos no DNA. I. Mata Atlântica – Estação Ecológica Juréia-Itatins

Débora Gomes Agripino^I; Marcos Enoque Leite Lima^II; Marcelo Rogério da Silva^I; Cristiane Infante Meda^I; Vanderlan da Silva Bolzani^III; Inês Cordeiro^I, Maria Claudia Marx Young^I, Paulo Roberto H. Moreno^II

^IInstituto de Botânica, CP 4005, 01061-970 São Paulo-SP, Brazil

^IIInstituto de Química, Universidade de São Paulo, CP 26077, 05513-970 São Paulo-SP, Brazil. Autor para Correspondência: Paulo Roberto H. Moreno

Tel: [phone], FAX: [phone]. E-mail: [e-mail].

^IIIInstituto de Química, Universidade Estadual Paulista, CP 355, 14800-900 Araraquara-SP, Brazil

ABSTRACT

I. Atlantic Rain Forest . Ecological Station Juréia-Itatins) Crude extracts from 88 plant species occurring in São Paulo State (Brazil), collected in an Atlantic Forest region, have been screened for antimicrobial and DNA-damaging activities. Of the 114 extracts assayed for antibacterial activity, only the extracts from leaves and stems of Aspidosperma ramiflorum (Apocynaceae) showed a slight activity against Escherichia coli. In the antifungal assay with Candida albicans, no active extract was observed, while in the bioautography assay with Cladosporium sphaerospermum and C. cladosporioides 12% were active. However, only the extract of Psychotria mapoureoides (Rubiaceae) stems showed a strong inhibition of both fungi. The DNA-damaging assay with mutant strains of Saccharomyces cerevisiae resulted in 17.5 % of active extracts. The majority (55 %) of the active extracts showed selectivity for the DNA-repair mechanism of topoisomerase II and only 20 % showed a selective response for the mechanism of topoisomerase I.

Key words: Atlantic Rain forest, Antibacterial activity, Antifungal activity, antitumoral activity, plants screening.

RESUMO

(Triagem de plantas nativas do Brasil para atividades antimicrobiana e de Danos no DNA I. Mata Atlântica . Estação Ecológica Juréia-Itatins). Oitenta e oito espécies nativas do estado de São Paulo foram coletadas numa região de Mata Atlântica e ensaiadas quanto a sua atividade antimicrobiana e capacidade de causar danos no DNA. Dos 114 extratos submetidos aos ensaios para atividade antibacteriana, apenas os extratos de folhas e galhos de Aspidosperma ramiflorum (Apocynaceae) apresentaram uma atividade fraca contra Escherichia coli. No ensaio antifúngico com Candida albicans, não foram observados extratos ativos. Por outro lado, no ensaio de bioautografia com Cladosporium sphaerospermum e C. cladosporioides 12% dos extratos apresentaram atividade. Contudo, nesse ensaio, somente o extrato dos ramos de Psychotria mapoureoides (Rubiaceae) inibiu fortemente o crescimento de ambas espécies do fungo. O ensaio para danos no DNA com cepas mutantes de Saccharomyces cerevisiae apresentou 17.5 % de extratos ativos. A maioria dos extratos ativos (55 %) apresentou resultados seletivos para danos dependentes da topoisomerase II como mecanismo de reparo do DNA e somente 20 % foram seletivos para o mecanismo da topoisomerase I.

Palavras-chave: Mata Atlântica, Atividade antibacteriana, Atividade antifúngica, Atividade antitumoral, Bioprospecção vegetal

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

References

1. ADJIBADE, Y., KUBALLA, B., CABALION, P., JUNG, M.L., BECK, J.P. & ANTON, R. 1989. Cytotoxicity on human leukemic and rat hepatoma cell lines of alkaloid extracts of Psychotria forsteriana. Planta Med. 55: 567-568.

2. ARISAWA, M., HANDA, S.S., MCPHERSON, D.D., LANKIN, D.C., CORDELL, G.A., FONG, H.H. & FARNSWORTH, N.R. 1984. Plant anticancer agents XXIX. Cleomiscosin A from Simaba multiflora, Soulamea soulameoides, and Matayba arborescens. J. Nat. Prod. 47: 300-307

3. BAURIN, N., ARNOULT, E., SCIOR, T., DO, Q.T. & BERNARD, P. 2002. Preliminary screening of some tropical plants for anti-tyrosinase activity. J. Ethnopharmacol. 82: 155-158.

4. CARVALHO, P.R.F. de, FURLAN, M., YOUNG, M.C.M., KINGSTON, D.G.I. & BOLZANI, V.S. 1998. Acetylated DNA-Damaging Clerodane Diterpenes from Casearia Sylvestris. Phytochemistry 49: 1659-1662.

5. CHO, J.Y., PARK, J., KIM, P.S., YOO, E.S., BAIK, K.U. & PARK, M.H. 2001. Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation. Biol. Pharm. Bull. 24: 167-171.

6. CONTE, L.A. 1996. Shaman pharmaceuticals. approach to drug development. In. Medicinal resources of the Tropical Forest - biodiversity and its importance to human health. (M.J. Balick, E. Elisabetsky & A.S. Laird, eds.). Columbia University Press, New York, p. 94-100.

7. DA SILVA, K.L., DOS SANTOS, A.R., MATTOS, P.E., YUNES, R.A., DELLE-MONACHE, F. & CECHINELFILHO, V. 2001. Chemical composition and analgesic activity of Calophyllum brasiliense leaves. Therapie 56:431-434.

8. DI STASI, L.C., OLIVEIRA, G.P., CARVALHAES, M.A., QUEIROZ-JUNIOR, M., TIEN, O.S., KAKINAMI, S.H. & REIS, M.S. 2002. Medicinal plants popularly used in the Brazilian Tropical Atlantic Forest. Fitoterapia 73: 69-91.

9. DORMAN, H.J.D. & DEANS, S.G. 2000. Antimicrobial agents from plants: antibacterial activity of plant volatile oils. J. Appl. Microbiol. 88: 308-316. http://www.biotaneotropica.org.br Moreno, P. R. H. (et al.) - Biota Neotropica, v4 (n2) - BN03804022004 14

10. GRAZZIOTIN, J.D., SCHAPOVAL, E.E., CHAVES, C.G., GLEYE, J. & HENRIQUES AT 1992. Phytochemical and analgesic investigation of Tabebuia chrysotricha. J. Ethnopharmacol. 36: 249-251.

11. GUNATILAKA, A.A.L, SAMARANAYAKE, G., KINGSTON, D.G.I, HOFFMANN, G. & JOHNSON, R.K. 1992. Bioactive ergost-5-ene-3ß,7a-diol derivatives from Pseudobersama mossambicensis. J. Nat. Prod. 55: 1648-1654.

12. HOMANS, A.L. & FUCHS, A. 1970. Direct bioautography on thin-layer chromatograms as a method for detecting fungitoxic substances. J. Chromatogr. 51: 327-329.

13. HONG, C.H., HUR, S.K., OH, O.J., KIM, S.S., NAM, K.A. & LEE, S.K. 2002. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J. Ethnopharmacol. 83:153-159.

14. JAGER, A.K., HUTCHINGS, A. & VAN STADEN, J. 1996. Screening of Zulu medicinal plants for prostaglandinsynthesis inhibitors. J. Ethnopharmacol. 52:95-100.

15. JAYASINGHE, U.L., JAYASOORIYA, C.P., BANDARA, B.M., EKANAYAKE, S.P., MERLINI, L. & ASSANTE, G. 2002. Antimicrobial activity of some Sri Lankan Rubiaceae and Meliaceae. Fitoterapia 73:24-427.

16. JESUS-MORAIS, C.M., ASSIS, E.F., CORDEIRO, R.S., BARBOSA-FILHO, J.M., LIMA, W.T., SILVA, Z.L., BOZZA, P.T. & CASTRO-FARIA-NETO, H.C. 2000. Yangambin, a lignan obtained from Ocotea duckei, differentiates putative PAF receptor subtypes in the gastrointestinal tract of rats. Planta Med. 66:211-216.

17. KERBER, V.A., GREGIANINI, T.S., PARANHOS, J.T., SCHWAMBACH, J., FARIAS, F., FETT, J.P., FETTNETO, A.G., ZUANAZZI, J.A., QUIRION, J.C., ELIZABETSKY, E. & HENRIQUES A.T. 2001. Brachycerine, a novel monoterpene indole alkaloid from Psychotria brachyceras. J. Nat. Prod. 64:677-679.

18. LOCHER, C.P., BURCH, M.T., MOWER, H.F., BERESTECKY, J., DAVIS, H., VAN POEL, B., LASURE A., VANDEN BERGHE, D.A. & VLIETINCK, A.J. 1995. Anti-microbial activity and anti-complement activity of extracts obtained from selected Hawaiian medicinal plants. J. Ethnopharmacol. 49:23-32.

19. LORDELLO, A.L.L., CAVALHEIRO, A.J., YOSHIDA, M. & GOTTLIEB, O.R. 2000 Phenylpropanoids, sterols and sesquiterpene from wood of Ocotea odorifera (Lauraceae). Rev Latinoam. Quim. 28:35-39.

20. LORENZO, D., LOAYZA, I., LEIGUE, L., FRIZZO, C., DELLACASSA, E. & MOYNA, P. 2001. Asaricin, the main component of Ocotea opifera Mart. essential oil. Nat. Prod. Lett. 15:163-170.

21. MARQUES, M.F.S., KATO, L., LEITÃO-FILHO, H.F. & REIS, F.A.M. (1996): Indole alkaloids from Aspidosperma ramiflorum. Phytochemistry 41:963-967.

22. MESIA-VELA, S., SANCHEZ, R.I,. ESTRADA-MUNIZ, E., ALAVEZ-SOLANO, D., TORRES-SOSA, C., JIMENEZ-ESTRADA, M., REYES-CHILPA, R. & KAUFFMAN F.C. 2001. Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1. Phytomedicine 8:481-488.

23. MORENO, P.R.H., VON POSER, G.L. & HENRIQUES, A.T. 1991. Atividade antimicrobiana e isolamento de alcalóides de Nectandra lanceolata. Rev. Bras. Farm. 72:27-28.

24. MORENO, P.R.H., VON POSER, G.L., RATES, S.M.K., YOSHIDA, M., GOTTLIEB, O.R. & HENRIQUES, A.T. 1993. Chemical constituents and antitumour activity of Nectandra grandiflora. Int. J. Pharmacognosy 31:189-192.

25. MYERS, N., MITTERMEIER, R.A., MITTERMEIER, C.G., FONSECA, G.A.B. & KENT, J. 2000. Biodiversity hotspots for conservation priorities. Nature 403:853-858.

26. PINTO, C.N., DANTAS, A.P., DE MOURA, K.C., EMERY, F.S., POLEQUEVITCH, P.F., PINTO, M.C., DE CASTRO, S.L. & PINTO, A.V. 2000. Chemical reactivity studies with naphthoquinones from Tabebuia with antitrypanosomal efficacy. Arzneimittelforschung 50:1120-1128.

27. RAHALISON L, HAMBURGER M, MONOD M, FRENK E, HOSTETTMANN K (1994): Antifungal tests in phytochemical investigations comparison of bioautographic methods using phytopatogenic and human pathogenic fungi. Planta Med 60: 41-44.

28. ROTH, A., KUBALLA, B., BOUNTHANH, C., CABALION, P., SEVENET, T., BECK, J.P. & ANTON, R. 1986. Cytotoxic activity of polyindoline alkaloids of Psychotria forsteriana (Rubiaceae):(1). Planta Med. Dec(6): 450-453.

29.S.M.A. . SECRETARIA DO MEIO AMBIENTE. 1996. Atlas das Unidades de Conservação do Estado de São Paulo. Parte 1. Litoral. Secretaria do Meio Ambiente, Secretaria de Energia, CESP, São Paulo. p.30.

30. SAI PRAKASH, C.V., HOCH, J.M. & KINGSTON, D.G.I. 2002. Structure and Stereochemistry of New Cytotoxic Clerodane Diterpenoids from the Bark of Casearia lucida from the Madagascar Rainforest. J. Nat. Prod. 65:100- 107.

31. SARTORI, N.T., CANEPELLE, D., DE SOUSA, P.T. JR. & MARTINS, D.T. (1999): Gastroprotective effect from Calophyllum brasiliense Camb. bark on experimental gastric lesions in rats and mice. J. Ethnopharmacol. 67:149-156.

32. TABARELLI, M., MANTOVANI, W. & PERES, C.A. 1999. Effects of habitat fragmentation on plant guild structure in the montane Atlantic forest of southeastern Brazil. Biol. Conserv. 91:119-127.

33. TERBORGH, J. & WINTER, B. 1980. Some causes of extinction. In. Conservation Biology: An Evolutionary-Ecological Perspective (M.E. SOULE & B.A. WILCOX, eds.). Sinauer Associates, Sunderland, p.119-133.

34. TILMAN, D., MAY, R.M., LEHMAN, C.L. & NOWAK, M.A. 1994. Habitat destruction and the extinction debt. Nature 371:65-66.

35. UEDA, S., UMEMURA, T., DOHGUCHI, K., MATSUZAKI, T., TOKUDA, H., NISHINO, H. & IWASHIMA, A. 1994. Production of anti-tumour-promoting furanonaphthoquinones in Tabebuia avellanedae cell cultures. Phytochemistry 36:323-325.

36. VEROTTA, L., PILATI, T., TATO, M., ELISABETSKY, E., AMADOR, T.A. & NUNES, D.S. 1998. Pyrrolidinoindoline Alkaloids from Psychotria colorata.

J. Nat. Prod. 61:392-396.

37. VERPOORTE, R., RUIGROK, C.L.M. & BAERHEIM SVENDSEN, A. 1982. Medicinal Plants of surinam II: Antimicrobial Active alkaloids from Aspidosperma marcgravianum. Planta Med. 46:149-152.

38. VERPOORTE, R., KOS-KUYCK, E., TIJN, A., TSOI, A., RUIGROK, C.L.M., DE JONG, G. & BAERHEIM SVENDSEN, A, 1983. Medicinal Plants of surinam III: Antimicrobially Active alkaloids from Aspidosperma excelsum. Planta Med. 48:283-289.

39. ZHOU, B.N., JOHNSON, R.K., MATTERN, M.R., WANG, X., HECHT, S.M., BECK, H.T., ORTIZ, A. & KINGSTON, D.G. 2000. Isolation and biochemical characterization of a new topoisomerase I inhibitor from Ocotea leucoxylon. J. Nat. Prod. 63:217-221.

Date Received : 05/19/2004

Revised:09/16/2004

Accepted: 09/30/2004

ISSN 1676-0611

References

• ¹ ADJIBADE, Y., KUBALLA, B., CABALION, P., JUNG, M.L., BECK, J.P. & ANTON, R. 1989. Cytotoxicity on human leukemic and rat hepatoma cell lines of alkaloid extracts of Psychotria forsteriana. Planta Med. 55: 567-568.
• ² ARISAWA, M., HANDA, S.S., MCPHERSON, D.D., LANKIN, D.C., CORDELL, G.A., FONG, H.H. & FARNSWORTH, N.R. 1984. Plant anticancer agents XXIX. Cleomiscosin A from Simaba multiflora, Soulamea soulameoides, and Matayba arborescens. J. Nat. Prod. 47: 300-307
• ³ BAURIN, N., ARNOULT, E., SCIOR, T., DO, Q.T. & BERNARD, P. 2002. Preliminary screening of some tropical plants for anti-tyrosinase activity. J. Ethnopharmacol. 82: 155-158.
• ⁴ CARVALHO, P.R.F. de, FURLAN, M., YOUNG, M.C.M., KINGSTON, D.G.I. & BOLZANI, V.S. 1998. Acetylated DNA-Damaging Clerodane Diterpenes from Casearia Sylvestris. Phytochemistry 49: 1659-1662.
• ⁵ CHO, J.Y., PARK, J., KIM, P.S., YOO, E.S., BAIK, K.U. & PARK, M.H. 2001. Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation. Biol. Pharm. Bull. 24: 167-171.
• ⁶ CONTE, L.A. 1996. Shaman pharmaceuticals. approach to drug development. In. Medicinal resources of the Tropical Forest - biodiversity and its importance to human health. (M.J. Balick, E. Elisabetsky & A.S. Laird, eds.). Columbia University Press, New York, p. 94-100.
• ⁷ DA SILVA, K.L., DOS SANTOS, A.R., MATTOS, P.E., YUNES, R.A., DELLE-MONACHE, F. & CECHINELFILHO, V. 2001. Chemical composition and analgesic activity of Calophyllum brasiliense leaves. Therapie 56:431-434.
• ⁸ DI STASI, L.C., OLIVEIRA, G.P., CARVALHAES, M.A., QUEIROZ-JUNIOR, M., TIEN, O.S., KAKINAMI, S.H. & REIS, M.S. 2002. Medicinal plants popularly used in the Brazilian Tropical Atlantic Forest. Fitoterapia 73: 69-91.
• ⁹ DORMAN, H.J.D. & DEANS, S.G. 2000. Antimicrobial agents from plants: antibacterial activity of plant volatile oils. J. Appl. Microbiol. 88: 308-316. http://www.biotaneotropica.org.br Moreno, P. R. H. (et al.) - Biota Neotropica, v4 (n2) - BN03804022004 14
• ¹⁰ GRAZZIOTIN, J.D., SCHAPOVAL, E.E., CHAVES, C.G., GLEYE, J. & HENRIQUES AT 1992. Phytochemical and analgesic investigation of Tabebuia chrysotricha. J. Ethnopharmacol. 36: 249-251.
• ¹¹ GUNATILAKA, A.A.L, SAMARANAYAKE, G., KINGSTON, D.G.I, HOFFMANN, G. & JOHNSON, R.K. 1992. Bioactive ergost-5-ene-3ß,7a-diol derivatives from Pseudobersama mossambicensis. J. Nat. Prod. 55: 1648-1654.
• ¹² HOMANS, A.L. & FUCHS, A. 1970. Direct bioautography on thin-layer chromatograms as a method for detecting fungitoxic substances. J. Chromatogr. 51: 327-329.
• ¹³ HONG, C.H., HUR, S.K., OH, O.J., KIM, S.S., NAM, K.A. & LEE, S.K. 2002. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J. Ethnopharmacol. 83:153-159.
• ¹⁴ JAGER, A.K., HUTCHINGS, A. & VAN STADEN, J. 1996. Screening of Zulu medicinal plants for prostaglandinsynthesis inhibitors. J. Ethnopharmacol. 52:95-100.
• ¹⁵ JAYASINGHE, U.L., JAYASOORIYA, C.P., BANDARA, B.M., EKANAYAKE, S.P., MERLINI, L. & ASSANTE, G. 2002. Antimicrobial activity of some Sri Lankan Rubiaceae and Meliaceae. Fitoterapia 73:24-427.
• ¹⁶ JESUS-MORAIS, C.M., ASSIS, E.F., CORDEIRO, R.S., BARBOSA-FILHO, J.M., LIMA, W.T., SILVA, Z.L., BOZZA, P.T. & CASTRO-FARIA-NETO, H.C. 2000. Yangambin, a lignan obtained from Ocotea duckei, differentiates putative PAF receptor subtypes in the gastrointestinal tract of rats. Planta Med. 66:211-216.
• ¹⁷ KERBER, V.A., GREGIANINI, T.S., PARANHOS, J.T., SCHWAMBACH, J., FARIAS, F., FETT, J.P., FETTNETO, A.G., ZUANAZZI, J.A., QUIRION, J.C., ELIZABETSKY, E. & HENRIQUES A.T. 2001. Brachycerine, a novel monoterpene indole alkaloid from Psychotria brachyceras. J. Nat. Prod. 64:677-679.
• ¹⁸ LOCHER, C.P., BURCH, M.T., MOWER, H.F., BERESTECKY, J., DAVIS, H., VAN POEL, B., LASURE A., VANDEN BERGHE, D.A. & VLIETINCK, A.J. 1995. Anti-microbial activity and anti-complement activity of extracts obtained from selected Hawaiian medicinal plants. J. Ethnopharmacol. 49:23-32.
• ¹⁹ LORDELLO, A.L.L., CAVALHEIRO, A.J., YOSHIDA, M. & GOTTLIEB, O.R. 2000 Phenylpropanoids, sterols and sesquiterpene from wood of Ocotea odorifera (Lauraceae). Rev Latinoam. Quim. 28:35-39.
• ²⁰ LORENZO, D., LOAYZA, I., LEIGUE, L., FRIZZO, C., DELLACASSA, E. & MOYNA, P. 2001. Asaricin, the main component of Ocotea opifera Mart. essential oil. Nat. Prod. Lett. 15:163-170.
• ²² MESIA-VELA, S., SANCHEZ, R.I,. ESTRADA-MUNIZ, E., ALAVEZ-SOLANO, D., TORRES-SOSA, C., JIMENEZ-ESTRADA, M., REYES-CHILPA, R. & KAUFFMAN F.C. 2001. Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1. Phytomedicine 8:481-488.
• ²⁴ MORENO, P.R.H., VON POSER, G.L., RATES, S.M.K., YOSHIDA, M., GOTTLIEB, O.R. & HENRIQUES, A.T. 1993. Chemical constituents and antitumour activity of Nectandra grandiflora. Int. J. Pharmacognosy 31:189-192.
• ²⁵ MYERS, N., MITTERMEIER, R.A., MITTERMEIER, C.G., FONSECA, G.A.B. & KENT, J. 2000. Biodiversity hotspots for conservation priorities. Nature 403:853-858.
• ²⁶ PINTO, C.N., DANTAS, A.P., DE MOURA, K.C., EMERY, F.S., POLEQUEVITCH, P.F., PINTO, M.C., DE CASTRO, S.L. & PINTO, A.V. 2000. Chemical reactivity studies with naphthoquinones from Tabebuia with antitrypanosomal efficacy. Arzneimittelforschung 50:1120-1128.
• ²⁷ RAHALISON L, HAMBURGER M, MONOD M, FRENK E, HOSTETTMANN K (1994): Antifungal tests in phytochemical investigations comparison of bioautographic methods using phytopatogenic and human pathogenic fungi. Planta Med 60: 41-44.
• ²⁸ ROTH, A., KUBALLA, B., BOUNTHANH, C., CABALION, P., SEVENET, T., BECK, J.P. & ANTON, R. 1986. Cytotoxic activity of polyindoline alkaloids of Psychotria forsteriana (Rubiaceae):(1). Planta Med. Dec(6): 450-453.
• ²⁹S.M.A. . SECRETARIA DO MEIO AMBIENTE. 1996. Atlas das Unidades de Conservação do Estado de São Paulo. Parte 1. Litoral. Secretaria do Meio Ambiente, Secretaria de Energia, CESP, São Paulo. p.30.
• ³⁰ SAI PRAKASH, C.V., HOCH, J.M. & KINGSTON, D.G.I. 2002. Structure and Stereochemistry of New Cytotoxic Clerodane Diterpenoids from the Bark of Casearia lucida from the Madagascar Rainforest. J. Nat. Prod. 65:100- 107.
• ³¹ SARTORI, N.T., CANEPELLE, D., DE SOUSA, P.T. JR. & MARTINS, D.T. (1999): Gastroprotective effect from Calophyllum brasiliense Camb. bark on experimental gastric lesions in rats and mice. J. Ethnopharmacol. 67:149-156.
• ³² TABARELLI, M., MANTOVANI, W. & PERES, C.A. 1999. Effects of habitat fragmentation on plant guild structure in the montane Atlantic forest of southeastern Brazil. Biol. Conserv. 91:119-127.
• ³³ TERBORGH, J. & WINTER, B. 1980. Some causes of extinction. In. Conservation Biology: An Evolutionary-Ecological Perspective (M.E. SOULE & B.A. WILCOX, eds.). Sinauer Associates, Sunderland, p.119-133.
• ³⁴ TILMAN, D., MAY, R.M., LEHMAN, C.L. & NOWAK, M.A. 1994. Habitat destruction and the extinction debt. Nature 371:65-66.
• ³⁵ UEDA, S., UMEMURA, T., DOHGUCHI, K., MATSUZAKI, T., TOKUDA, H., NISHINO, H. & IWASHIMA, A. 1994. Production of anti-tumour-promoting furanonaphthoquinones in Tabebuia avellanedae cell cultures. Phytochemistry 36:323-325.
• J. Nat. Prod. 61:392-396.
• ³⁷ VERPOORTE, R., RUIGROK, C.L.M. & BAERHEIM SVENDSEN, A. 1982. Medicinal Plants of surinam II: Antimicrobial Active alkaloids from Aspidosperma marcgravianum. Planta Med. 46:149-152.
• ³⁸ VERPOORTE, R., KOS-KUYCK, E., TIJN, A., TSOI, A., RUIGROK, C.L.M., DE JONG, G. & BAERHEIM SVENDSEN, A, 1983. Medicinal Plants of surinam III: Antimicrobially Active alkaloids from Aspidosperma excelsum. Planta Med. 48:283-289.
• ³⁹ ZHOU, B.N., JOHNSON, R.K., MATTERN, M.R., WANG, X., HECHT, S.M., BECK, H.T., ORTIZ, A. & KINGSTON, D.G. 2000. Isolation and biochemical characterization of a new topoisomerase I inhibitor from Ocotea leucoxylon. J. Nat. Prod. 63:217-221.

Publication Dates

• Publication in this collection
  12 June 2013
• Date of issue
  2004

History

• Accepted
  30 Sept 2004
• Received
  19 May 2004
• Reviewed
  16 Sept 2004