title: Synthesis and antimalarial evaluation of novel isocryptolepine derivatives.
abstract: A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and for cytotoxicity (3T3 cells). Di-halogenated compounds were the most potent derivatives and 8-bromo-2-chloroisocryptolepine displayed the highest selectivity index (106; the ratio of cytotoxicity (IC(50)=9005 nM) to antimalarial activity (IC(50)=85 nM)). Our evaluation of novel isocryptolepine compounds has demonstrated that di-halogenated derivatives are promising antimalarial lead compounds.
authors: School of Pharmacy, Curtin University, Bentley, GPO Box U1987, Perth, Western Australia 6845, Australia.
authors: Louise R
authors: LR
authors: Whittell
authors: Kevin T
authors: KT
authors: Batty
authors: Rina P M
authors: RP
authors: Wong
authors: Erin M
authors: EM
authors: Bolitho
authors: Simon A
authors: SA
authors: Fox
authors: Timothy M E
authors: TM
authors: Davis
authors: Paul E
authors: PE
authors: Murray
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D026121:Indole Alkaloids; D011804:Quinolines; C024015:cryptolepine; D002738:Chloroquine