Quinoline-pyrimidine hybrids: synthesis, antiplasmodial activity, SAR, and mode of action studies
Singh, Kamaljit × Kaur, Hardeep Smith, Peter de Kock, Carmen Chibale, Kelly Balzarini, Jan #
Journal of Medicinal Chemistry vol:57 issue:2 pages:435-48
For the treatment of malaria which affects nearly 200 million people each year and the continued exacerbation by the emergence of drug resistance to most of the available antimalarials, the "covalent bitherapy" suggests hybrid molecules to be the next-generation antimalarial drugs. In this investigation, new hybrids of 4-aminoquinoline and pyrimidine moieties that show antiplasmodial activity in the nM range against chloroquine-resistant as well as chloroquine-sensitive strains of Plasmodium falciparum have been prepared. Cytotoxicity evaluation and mode of action of most potent hybrid molecule have been conducted.