ABSTRACT
A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) < 10 µM). Oxiranes 6 and 25, prepared respectively by reaction of α-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule.
Subject(s)
Antimalarials/chemical synthesis , Antimalarials/pharmacology , Ethylene Oxide/chemistry , Ethylene Oxide/pharmacology , Plasmodium falciparum/drug effects , Quinones/chemical synthesis , Quinones/pharmacology , Antimalarials/chemistry , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Ethylene Oxide/chemical synthesis , Fibroblasts/drug effects , Humans , Molecular Structure , Parasitic Sensitivity Tests , Quinones/chemistry , Structure-Activity RelationshipABSTRACT
The central six-membered ring in the title compound, C(16)H(16)O(3), is almost planar (and almost coplanar with the aromatic ring), despite one of its C atoms being formally sp(3) hybridized. The planarity is a consequence of the C atom at the centre of the spirocyclic system also being part of the three-membered epoxide ring. The molecules are linked by pi-pi and C-H.pi interactions.
