Synthesis of 4-aminoquinoline–pyrimidine hybrids as potent antimalarials and their mode of action studies

•New hybrids of 4-aminoquinoline and pyrimidine were synthesized efficaciously.•nM range antiplasmodial activity.•Activity against both CQS and CQR strains of Plasmodium falciparum.•Effective binding to heme as well as AT rich pUC18 DNA.

One of the most viable options to tackle the growing resistance to the antimalarial drugs such as artemisinin is to resort to synthetic drugs. The multi-target strategy involving the use of hybrid drugs has shown promise. In line with this, new hybrids of quinoline with pyrimidine have been synthesized and evaluated for their antiplasmodial activity against both CQS and CQR strains of Plasmodium falciparum. These depicted activity in nanomolar range and were found to bind to heme as well as AT rich pUC18 DNA.

Graphical abstractEfficaciously synthesized new 4-aminoquinoline–pyrimidine hybrids depict antiplasmodial activity (nM) against CQR and CQS strains of Plasmidum falciparum. Representative compounds revealed binding with heme and AT rich pUC18 DNA, spectrophotometically.Figure optionsDownload full-size imageDownload as PowerPoint slide