Nitrile and amide integrated pyrazole based molecular hybrids: Synthesis, biological evaluation, and molecular docking studies

A group of new nitrile- and carboxamide-tethered pyrazole derivatives (6a-6g) was successfully synthesized from arylhydrazines and ketones having aryl and alkyl groups using a multi-stage synthesis technique. Of the hybrids studied, the compound 6d, which has a para-fluorophenyl group on the pyrazole core, displayed the maximum antioxidant activity (∼83 %) in the DPPH radical-scavenging evaluation, which is comparable with that of the standard, ascorbic acid. Interestingly, it appears that the hybrid 6d also demonstrated improved cytotoxicity against both cell types of pancreatic cancer, SW1990 and AsPC1 (IC₅₀ values of 18 μM and ∼25 μM, respectively). The activity of 6d is superior to that of the activity of the standard drug, gemcitabine, against both SW1990 and AsPC1 cancer cells. Molecular docking experiments further confirmed its potential, demonstrating a strong binding affinity to the protein, BCL-2 (−8.3 kcal/mol). The current study's findings suggest that the hybrid 6d is a promising candidate and that its structure could serve as a helpful model for developing more potent bioactive compounds.