Novel Thiazolidinone/Thiazolo[3,2-]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation.

In connection with our research program on the development of new isatin-based anticancer candidates, herein we report the synthesis of two novel series of thiazolidinone-isatin conjugates (⁻) and thiazolo[3,2-]benzimidazolone-isatin conjugates (⁻), and in vitro evaluation of their antiproliferative activity towards two breast cancer cell lines; triple negative MDA-MB-231, and MCF-7. Compounds and emerged as the most active congeners against MDA-MB-231 cells (IC = 7.6 ± 0.5 and 13.2 ± 1.1 µM, respectively). Compounds and were able to provoke apoptosis in MDA-MB-231 cells, evidenced by the up-regulation of Bax and down-regulation of Bcl-2, besides boosting caspase-3 levels. Hybrid induced a fourfold increase in the percentage of cells at Sub-G₁, with concurrent arrest in G₂-M phase by 2.5-folds. Furthermore, hybrid resulted in a sixfold increase in the percentage of annexin V-FITC positive apoptotic MDA-MB-231 cells as compared with the control. Moreover, the cytotoxic activities of the active conjugates were assessed towards two nontumorigenic cell lines (breast MCF-10A and lung WI-38) where both conjugates and displayed mean tumor selectivity index: 9.6 and 13.9, respectively. Finally, several ADME descriptors were predicted for the active conjugates via a theoretical kinetic study.