Exploring Benzothiazole-Pyrazole Hybrids as Anticancer Agents: Synthesis, In Vitro Testing, Molecular Docking and Dynamic Simulation Study

Abstract

In this study, we present comprehensive work on synthesis, and anticancer evaluation of a new series of benzothiazole-pyrazole hybrids. The structures of the synthesized compounds were confirmed using a comprehensive suite of analytical techniques, including ¹H, ¹³C NMR, FT-IR, and HRMS. Among the series, the hybrid compound featuring a para-fluorophenyl substituent on the pyrazole ring exhibited notable in vitro anticancer activity compared to standard 5-fluorouracil against the MCF-7 cell line. To support the experimental findings, in silico studies were performed using physics-based approaches such as AutoDock Vina, molecular dynamics (MD) simulations, and MM-GBSA calculations. These studies revealed strong binding affinity of the compound toward the target protein (PDB ID: 4AGC), with key interactions involving amino acid residues ALA113A, ILE120A, LEU121A, ILE124A, LEU201A, and ILE226A. Overall, this compound emerges as a promising lead candidate for further development in anticancer drug discovery.