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 IC₅₀ 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 IC₅₀ (0.439 mM). Compound 5k with IC₅₀ value of 0.765 mM was found to be the most potent antiproliferative agent for the HeLa cancer cells. Moreover, hybrid molecule 5f with IC₅₀ value of 0.706 mM exhibited better inhibitory activity against A549 cancer cells in comparison to the reference carboplatin drug having IC₅₀ (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.