Activity of coumarin extracts from leaves of Calophyllum brasiliense on Leishmania braziliensis

M. A. Brenzan; C. I. P. Ferreira; V. M. C. Lonardoni; P. A. Honda; R. F. Edson; C. V. Nakamura; B. P. D. Filho; T. Ueda-Nakamura; D. A. G. Cortez

doi:10.1055/s-0028-1084178

Activity of coumarin extracts from leaves of Calophyllum brasiliense on Leishmania braziliensis

MA Brenzan ¹, CIP Ferreira ¹, VMC Lonardoni ², PA Honda ², RF Edson ³, CV Nakamura ², BPD Filho ², T Ueda-Nakamura ², DAG Cortez ¹

¹Departamento de Farmácia e Farmacologia, Universidade Estadual de Maringá, Av. Colombo, 5790, Campus Universitário, 87020–900 Maringá – PR, Brazil.
²Departamento de Análises Clínicas, Universidade Estadual de Maringá, Av. Colombo, 5790, Campus Universitário, 87020–900 Maringá – PR, Brazil.
³Departamento de Química, Universidade Federal de São Carlos, CP 676, 13565–905 São Carlos – SP, Brazil

Abstract

Leishmania braziliensis is the most common etiologic agent of leishmaniasis [1] which is an endemic disease in South America. In our previous studies, Calophyllum brasiliense showed activity against Leishmania amazonensis [2]. In the present study, we evaluated the activity of extracts and (-) mammea A/BB from leaves of Calophyllum brasiliense Camb. (Clusiaceae), against Leishmania braziliensis. The dichloromethane extract and coumarin (-) mammea A/BB showed significant activity against the promastigote forms of L. braziliensis, with 50% lethal dose (LD₅₀) at concentrations of 60 and 23.2µg/mL, respectively. However, the aqueous extract from the leaves and amentoflavone showed no activity against promastigote forms; both of them showed LD₅₀>320µg/mL. For the intracellular amastigote forms, the dichloromethane extract and coumarin (-) mammea A/BB reduced by 50% the infection index of parasites in macrophages at concentrations of 22 and 29µg/mL, respectively. In addition, the dichloromethane extract showed no cytotoxic effects on mouse peritoneal macrophages at concentrations up to 1000µg/mL. On the other hand, coumarin (-) mammea A/BB showed more cytotoxicity than the dichloromethane extract: coumarin inhibited the growth of mouse peritoneal macrophages by 29.7% at concentrations of 80µg/mL. The compounds were characterized by one- and two-dimensional ¹H and ¹³C NMR analyses. These results provide new perspectives on the development of novel drugs with leishmanicidal activity obtained from natural products.

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

References: 1. Grevelink, SA., Lerner EA (1996)J. Am. Acad. Dermatol. 34:257–272. 2. Brenzan, MA. et al. (2007) Parasitol. Res. 101:715–722.