Planta Med 2008; 74 - PG28
DOI: 10.1055/s-0028-1084781

Structure-activity relationship of (-) mammea A/BB derivatives against Leishmania amazonensis

MA Brenzan 1, CV Nakamura 2, BPD Filho 2, T Ueda-Nakamura 2, MCM Young 3, JA Júnior 4, AG Corrêa 4, DAG Cortez 5
  • 1Pós Graduação em Ciências Farmacêuticas
  • 2Laboratório de Microbiologia Aplicada aos Produtos Naturais e Sintéticos, Departamento de Análises Clínicas, Universidade Estadual de Maringá
  • 3Instituto de Botânica de São Paulo
  • 4Departamento de Química, Universidade Federal de São Carlos
  • 5Departamento de Farmácia e Farmacologia, Universidade Estadual de Maringá, Av. Colombo 5790, 87020–900, Maringá, PR, Brazil

We studied the structure-activity relationship of coumarin (-) mammea A/BB isolated from the CH2Cl2 extract of Calophyllum brasilense leaves, against Leishmania amazonensis. In our previous studies, Calophyllum brasiliense showed activity against L. amazonensis [1] and Leishmania braziliensis [2]. Thus, we evaluated the antileishmanial activity of natural, synthetic and derivatives of this coumarin, against promastigote forms of L. amazonensis, and their cytotoxicity on J774G8 murine macrophages. The derivatives were obtained by hydrogenation and methoxylation reactions. The compound structures were elucidated on the basis of spectroscopic data. The compounds 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one, 7-hydroxy-5-methoxy-8-(2-methylbutanoyl)-6-(3-methylbut-2-en-1-yl)-4-phenylcoumarin and 5,7-dimethoxy-8-(1-methoxy-2-methylbutyl)-6-(3-methylbut-2-en-1-yl)-4 phenylcoumarin were more biologically active than the compound (-) mammea A/BB (3.0µg/mL), with IC50 values of 0.37; 1.02; 0.87µg/mL respectively; of these, the compound 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one displayed the highest activity. On the other hand, the compounds mammea B/BB; 5,7-dimethoxy-8-(2-methylbutanoyl)-6-(3-methylbut-2-en-1-yl)-4-phenylcoumarin and 5,7-dihydroxy-4-phenylcoumarin were less active than (-) mammea A/BB, with IC50 of 11.21; 6.57; 15.29µg/mL respectively; 5,7-dihydroxy-4-phenylcoumarin showed the lowest antileishmanial activity of all. This study has contributed to the study of the structure and activity of (-) mammea A/BB, and it is part of a continued search for new drugs with high activity and low side effects against diseases associated with protozoan parasites, such as leishmaniasis.

Acknowledgements: This study was supported through grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and CAPES.

References: 1. Brenzan, M.A. et al. (2007) Parasitol Res 101: 715–722

2. Brenzan, M.A. et al. (2008) Pharm Biol in press