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.
Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226001, India. sashidhar123@gmail.com
Koneni V
KV
Sashidhara
Suriya P
SP
Singh
Shiv Vardan
SV
Singh
Rajeev K
RK
Srivastava
Kumkum
K
Srivastava
J K
JK
Saxena
Sunil K
SK
Puri
D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006420:Hemeproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D031308:Salicaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D006027:Glycosides; D006420:Hemeproteins; D010636:Phenols; C020753:hemozoin