Antiparasitic activity of flavonoids from Piper species

Abstract

Parasitic diseases, including leishmaniasis, chagas and malaria, are serious problems for public health throughout the world, especially in tropical and subtropical regions [1]. Due to the absence of effective vaccines, inadequate chemotherapy and the emergence of drug resistance, currently, there is an urgent need to search for novel, effective and safe drugs for the treatment of these diseases [2]. Several Piper species have been used in the traditional medicine in Latin America, including for the treatment of parasitic diseases [3]. As part of our research aiming to uncover antiparasitic compounds from Bolivian Piper species, we studied the dichloromethane extract from the leaves of Piper aduncum, P. acutifolium, P. glabratum, P. heterophyllum, P. pilliraneum and P. rusbyi. This study has led to the isolation of eight known flavonoids and a new compound, 5,5′-dihydroxy-7,3′-dimethoxy-flavanone. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC and HMBC). In the search for new antiparasitic agents, these compounds were evaluated in vitro against three strains of Leishmania (L. amazonensis, L. braziliensis and L. donovani), Trypanosoma cruzi and Plasmodium falciparum. 4′,7-Dimethoxy-5-hydroxy-flavanone (IC50 4.0µg/mL) showed a moderate activity against P. falciparum. The most active compound against promastigote forms of the three Leishmania strains was flavokavain B (IC50 5.4µg/mL), with twice the activity of the control pentamidine (IC50 10.0µg/mL). These results support the use of Piper species as a traditional remedy in the treatment of parasitic diseases.