RESUMEN
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.
Asunto(s)
Antimaláricos/síntesis química , Antimaláricos/farmacología , Óxido de Etileno/química , Óxido de Etileno/farmacología , Plasmodium falciparum/efectos de los fármacos , Quinonas/síntesis química , Quinonas/farmacología , Antimaláricos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Óxido de Etileno/síntesis química , Fibroblastos/efectos de los fármacos , Humanos , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Quinonas/química , Relación Estructura-ActividadRESUMEN
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.
