Facile Synthesis, Characterization and in vitro Biological Evaluation of a Series of Sulfonylurea-linked Quinoline Derivatives as Potential Antimalarial Agents

Abstract

World Health Organization (WHO) statistics showed that malaria has still remained a global threat due to its steady increase in deaths across the globe. Due to the necessity for novel pharmaceuticals, researchers discovered that a hybrid pharmacophore-designed methodology would be an effective means to develop new synthetic compounds and evaluate their efficacy against malaria. Therefore, a series of sulfonylurea-linked quinolines (C1-C6) were synthesized and evaluated for their in vitro antimalarial properties against Plasmodium falciparum. All the compounds (C1-C6) were screened through in vitro bioassays to assess their antimalarial potential against P. falciparum strain to identify the bioactive hit molecule; compounds were relatively compared with the clinically proven antimalarial agent e.g. artesunate. Based on the results, structure-activity relationships (SARs) have been derived that can be applied to design more analogues. Among the compounds tested, C3 and C2 were reported to be the most potent compounds with 68.10% and 65.55% inhibition of parasitemia in infected red blood cells (iRBC) compared to the positive standard artesunate with 64.98%, respectively. The in vitro antimalarial properties of compounds C3 and C2 were assumed to be primarily due to the presence of complementary pharmacophoric features such as sulfonylurea and quinoline, which formed part of the basic scaffold that was earlier independently well established as antimalarial pharmacophores.