Leishmanicidal, Antiplasmodial and Cytotoxic Activity of Indole Alkaloids from Corynanthe pachyceras

Abstract

Five indole alkaloids, corynantheidine, corynantheine, dihydrocorynantheine, α-yohimbine and corynanthine were isolated from bark of Corynanthe pachyceras K. Schum. (Rubiaceae). The structures were established by spectroscopic methods, inlcuding previously unreported assignment of all ¹H-NMR resonances by COSY and NOESY experiments. These and related alkaloids showed pronounced activity against Leishmania major promastigotes (IC₅₀ at the micromolar level) but no significant in vitro antiplasmodial activity (against chloroquine-sensitive Plasmodium falciparum). Cytotoxicity assessed with drug sensitive KB-3-1 and multidrug-resistant KB-V1 cell lines was low; the alkaloids are apparently not substrates for the P-glycoprotein (P-170) efflux pump.

Key words

Indole alkaloids - Plasmodium - Leishmania - multi-drug resistance - NMR

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