Synthesis, anticancer evaluation, in‐silico ADMET and molecular docking studies for tailored pyrazolo‐benzothiazole hybrids

Abstract The present article demonstrates the regioselective synthesis, characterization, and biological evaluation of eighteen novel pyrazolo‐benzothiazole hybrid molecules 5a–5r. We have utilized β,β‐ditosyloxy ketone protocol to synthesize these hybrid molecules. The synthesized compounds were tested for their in‐vitro antiproliferative activities using MTT assay against breast cancer (MCF‐7), cervical cancer (HeLa), and Lung cancer (A549) cell lines. Hybrid molecules 5a, 5m, 5n, and 5o with IC 50 values of 0.359 mM, 0.051 mM, 0.079 mM, and 0.259 mM respectively exhibited admirable growth inhibitory properties against MCF‐7 cancer cells which are even better than reference carboplatin drug having IC 50 (0.439 mM). Compound 5k with IC 50 value of 0.765 mM was found to be the most potent antiproliferative agent for the HeLa cancer cells. Moreover, hybrid molecule 5f with IC 50 value of 0.706 mM exhibited better inhibitory activity against A549 cancer cells in comparison to the reference carboplatin drug having IC 50 (0.805 mM). The mechanism of cellular toxicity was studied using the Annexin V‐FITC/PI double staining method and cell cycle assay. Molecular docking studies for all the synthesized compounds have also been performed in the binding pocket of VEGFR2 sites (PDB code: 4ASD). Finally, the ADMET profile of the potent molecules was investigated to predict their drug‐likeness behaviour.