Molecular Hybrids Integrated with Benzimidazole and Pyrazole Structural Motifs: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies

Abstract

Synthesis of a series of benzimidazole-ornamented pyrazoles, <b>6a-6j</b> has been obtained from arylhydrazine and aralkyl ketones via a multistep synthetic strategy. Among them, a hybrid-possessing <i>para</i>-nitrophenyl moiety connected to a pyrazole scaffold (<b>6a</b>) exerted the highest anti-inflammatory activity, which is superior to the standard, diclofenac sodium. While executing the 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, a hybrid-possessing <i>para</i>-bromophenyl unit integrated at the pyrazole structural motif (<b>6i</b>) exhibited the highest activity among the hybrids examined. Besides, evaluation of anticancer potency of the synthesized hybrids revealed that the one containing a <i>para</i>-fluorophenyl unit tethered at the pyrazole nucleus (<b>6h</b>) showed the highest activity against both the pancreatic cancer cells (SW1990 and AsPCl) investigated. Considerable binding affinity between B-cell lymphoma and the hybrid, <b>6h</b> has been reflected while performing molecular docking studies (-8.65 kcal/mol). The outcomes of the investigation expose that these hybrids could be used as effective intermediates to construct more potent biological agents.