Isolation and identification of β-hematin inhibitors from Flacourtia indica as promising antiplasmodial agents

An ethanolic extract (A001) of the leaves and twigs of Flacourtia indica (Burm.f.) Merr., was purified to give a new phenolic glycoside, 2-(2-benzoyl-β-d-glucopyranosyloxy)-7-(1α,2α,6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol (1) together with poliothrysoside (2), catechin-[5,6-e]-4β-(3,4-dihydroxyphenyl)dihydro-2(3H)-pyranone (3), 2-(6-benzoyl-β-d-glucopyranosyloxy)-7-(1α,2α,6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol (4), chrysoeriol-7-O-β-d-glucopyranoside (5), and mururin A (6). Compound 6 significantly inhibited the in vitro growth of both a chloroquine-sensitive (3D7) and a chloroquine-resistant (K1) strain of Plasmodium falciparum. It forms a complex with hematin and inhibits β-hematin formation, suggesting that this compound act on a heme polymerization target.

A phenylpropanoid catechin 6 isolated from Flacourtia indica exhibited significant antiplasmodial activity against a chloroquine-resistant (K1) strain. It also inhibited β-hematin formation and showed protection against H2O2-mediated hemin degradation.Figure optionsDownload as PowerPoint slideHighlights
► A new phenolic glycoside 1 together with five known compounds was isolated from F. indica.
► Phenylpropanoid catechin 6 emerged as a lead molecule, active against both strains of P. falciparum.
► It inhibited β-hematin formation and gave protection against H2O2-mediated hemin degradation.
► Phenylpropanoid catechins emerged as a new class of antiplasmodial agents.