Design, Synthesis, Antitumor, and Antiplasmodial Evaluation of New 7-Chloroquinoline-Benzimidazole Hybrids.

Newly synthesized 7-chloro-4-aminoquinoline-benzimidazole hybrids were characterized by NMR and elemental analysis. Compounds were tested for their effects on the growth of the non-tumor cell line MRC-5 (human fetal lung fibroblasts) and carcinoma (HeLa and CaCo-2), leukemia, and lymphoma (Hut78, THP-1, and HL-60) cell lines. The obtained results, expressed as the concentration at which 50% inhibition of cell growth is achieved (IC 50 value), show that the tested compounds affect cell growth differently depending on the cell line and the applied dose (IC 50 ranged from 0.2 to >100 µM). Also, the antiplasmodial activity of these hybrids was evaluated against two P. falciparum strains ( Pf 3D7 and Pf Dd2). The tested compounds showed potent antiplasmodial activity, against both strains, at nanomolar concentrations. Quantitative structure-activity relationship (QSAR) analysis resulted in predictive models for antiplasmodial activity against the 3D7 strain ( R 2 = 0.886; R ext 2 = 0.937; F = 41.589) and Dd2 strain ( R 2 = 0.859; R ext 2 = 0.878; F = 32.525) of P. falciparum . QSAR models identified the structural features of these favorable effects on antiplasmodial activities.