Design, synthesis and biological evaluation of indazole carboxamide analogues as potential anticancer agents

Novel indazole carboxamides (3a-j) were synthesized using conventional, catalytic, and green methods. Their anti-proliferative activities were evaluated through in vitro and in silico investigations. Among the three synthetic methods, green method proved to be the most efficient with an average reaction time 15 minutes, 80% yield on an average, maintaining room temperature in all the cases. Initial in vitro anticancer studies using the MTT colorimetric assay were performed on three human cancer cell lines (MCF-7, HeLa, and SKBR-3) to assess the therapeutic efficacy of the synthesized compounds. Compound 3j showed high potency growth inhibitory activity across the three cell lines (IC50=3 mu M, 2 mu M, and 4 mu M). In fact, this compound showed higher activity against HeLa as compared to that of Nocodazole (IC50 = 1.1 mu M, 3.2 mu M, and 2.4 mu M) taken as the reference drug. Additionally, computational studies, including molecular docking and simulations, were performed to assess the binding affinity of compounds against the 7Z2P receptor. Notably, all the compounds demonstrated excellent binding energy with a range of -8.05 to -9.91 kcal/mol. Further, the 7Z2P-3j complex was subjected to a 100 ns MD simulation to evaluate the stability of the complex. The in vitro, molecular docking, and pharmacokinetic profile underscored the potential of Indazole Carboxamides as promising anticancer agents. In view of the N and S containing heterocyclic nature of the synthesised compounds, as a future course, it is envisaged to carry out their antimicrobial activities too.