Pyrimidine-chloroquinoline hybrids: Synthesis and antiplasmodial activity

Abstract

Triazole tethered 7-chloroquinoline-pyrimidine-5-carboxylate hybrids were synthesized and evaluated for antiplasmodial activity against chloroquine sensitive (CQ^S) NF54 strain of Plasmodium falciparum. The most active hybrids of the series were further screened against the chloroquine resistant (CQ^R) Dd2 strain of the parasite and for in vitro cytotoxicity against mammalian Vero cell lines. Further, their physico-chemical properties, binding studies with hemin (monomeric &μ-oxo dimeric) and DNA [pUC-18, calf thymus (CT)] led us to plausible proposed binding mode of the most active member of the present series.

Keywords: 7-Chloroquinoline; Antiplasmodial studies; Binding with DNA; Huisgen 1,3-dipolar cycloaddition; Lipophilicity; Pyrimidine hybrids; Triazole.