Benzothiazole-triazole hybrids: Novel anticancer agents inducing cell cycle arrest and apoptosis through Bcl-2 inhibition in triple-negative breast cancer.

In this study, we aim to detail the design and synthesis of a series of benzothiazole tethered triazole compounds that incorporate acetamide chains, with the purpose of investigating their potential as anticancer agents. The structural integrity of the compounds was confirmed through characterization using H NMR, C NMR, mass spectrometry, and IR spectroscopy. The compounds demonstrated notable cytotoxic effects when tested against a range of cancer cell lines, with a specific inhibition observed in triple-negative breast cancer. Among the compounds, the one with trichloro substitution demonstrated the highest potency, as indicated by an IC value of 30.49 μM. The compounds were found to trigger cell cycle arrest in the G2/M phase and promote apoptosis, as observed in the mechanistic studies. The Bcl-2 protein exhibited significant binding interactions in molecular docking studies, which were then corroborated through molecular dynamics simulations spanning 100 ns. The simulations confirmed the stability of the ligand-protein complex, as supported by RMSD, RMSF, and hydrogen bond analyses, reinforcing the proposed mechanism of Bcl-2-mediated apoptosis.