Design, synthesis, and in silico-in vitro antimalarial evaluation of 1,2,3-triazole-linked dihydropyrimidinone quinoline hybrids

Abstract In response to the malaria parasite’s resistance towards quinoline-based antimalarial drugs, we have employed quinoline-containing compounds in combination with dihydropyrimidinone (DHPM) analogues as reversal agents (RAs) and investigated their activities based on DHPM’s abilities. The present study click chemistry link DHPM quinoline which offered several synthetic advantages over previously used amide coupling for same hybrids. Among synthesised compounds, 4 hybrids 7-chloroquinoline moiety showed activity below 1 µM while mefloquine lower than chloroquine (CQ) tested IC 50 determination, four displayed good increased sensitivity against CQ-resistant K1 strain between 421 567 nM higher 138 245 NF54 CQ-sensitive strain, three values greater 5 µM. Additionally, silico molecular docking dynamics studies were conducted investigate binding affinities of all glutathione reductase protein competitive inhibitors. Further optimisation compound highest affinity generated 16 flavine adenine dinucleotide (FAD) cofactor.