Potent antiplasmodial agents in Carica papaya L.

Abstract

Decoctions of papaya leaves have been used in Indonesia as a traditional remedy to prevent and treat malaria [1]. With the aim to validate the traditional use we tested a methanolic extract of Carica papaya L. against Plasmodium falciparum (K1 strain) in vitro. This extract inhibited the growth of the parasites by 51% at a test concentration of 4.8 µg/ml. HPLC-based activity profiling located the active compounds in the extract as alkaloids. After enrichment of these alkaloids with cationic ion exchange resin and separation of the alkaloidal fraction with ELSD-triggered flash chromatography, we successfully isolated five piperidine alkaloids. By means of spectroscopic and computational methods, corroborated by X-ray analysis, the structures of (-)-carpamic acid, (+)-methyl carpamate, (+)-carpaine [2], along with a (+)-stereoisomer of carpaine and a (+)-derivative of carpaine produced by monomethanolysis were identified. When tested against Plasmodium falciparum (K1 strain), (+)-carpaine (IC50 of 0.21µM, selectivity index of 98) showed the most potent and selective antiplasmodial in vitro activity amongst the isolated compounds. Despite this very promising result, in vivo testing of carpaine in a murine model (daily dose of 10 mg/kg BW intraperitoneally) did not reduce parasitemia until day 10 after infection.