Triazole tethered 7-chloroquinoline-pyrimidine-5-carboxylate hybrids were synthesized and evaluated for antiplasmodial activity against chloroquine sensitive (CQS) NF54 strain of Plasmodium falciparum. The most active hybrids of the series were further screened against the chloroquine resistant (CQR) 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.