Design, Discovery, Synthesis, Molecular Docking, MD Simulation, and In Vitro Biological Evaluation of Thiazolidinedione-Clubbed Benzimidazole Hybrids as Potential Anticancer Agents.

Authors

Pragya Dubey, DharamPal Pathak, Archana Sharma, Satyam Sharma, Garima Chauhan, Md Azhar Iqbal, Rajeev Taliyan, Shobha Kumari

Published in

Medicinal chemistry (Shariqah (United Arab Emirates)). Sep 30, 2026. Epub Sep 30, 2026.

Abstract

Breast cancer is a major global health issue. A new series of thiazolidinedione-benzimidazole hybrid derivatives (TBZ1-15) was developed and tested for anticancer properties against the MCF-7 breast cancer cell line using the MTT assay. Among these compounds, TBZ-13 showed the greatest cytotoxicity, with an IC₂⁽ of 35 μM.
To further elucidate its mechanism of action, TBZ-13 was subjected to multiple in vitro assays, including colony formation, Hoechst staining, reactive oxygen species (ROS) generation, cell migration, and propidium iodide (PI) staining. The results demonstrated that TBZ- 13 significantly inhibits clonogenic survival and cell migration, while inducing pronounced nuclear condensation and fragmentation, confirming apoptosis. Moreover, TBZ-13 caused a marked increase in intracellular ROS levels, indicating that oxidative stress-mediated cytotoxicity is a leading mechanism of cytotoxicity.
Notably, TBZ-13 outperformed the reference drug troglitazone in suppressing metastatic potential and promoting cancer cell death. Molecular docking studies were conducted to investigate interactions with peroxisome proliferator-activated receptor gamma (PPAR-γ), a key target implicated in tumor progression, angiogenesis, and metastasis. The crystal structure of human PPAR-γ (PDB ID: 1FM9; resolution 2.10 Å) was used for docking analysis. TBZ-13 displayed favorable binding conformations with critical hydrogen bonding interactions involving Tyr473, His323, and Ser289. Overall, these findings suggest that TBZ-13 is a promising anticancer lead candidate for further development.
The study focuses on breast cancer, a leading cause of death globally, introducing a series of thiazolidinedione-benzimidazole hybrid derivatives (TBZ1-15) evaluated for anticancer activity against the MCF-7 cell line. TBZ-13 showcased the highest cytotoxicity with an IC₂⁽ of 35 μM. Subsequent in vitro assays revealed that TBZ-13 inhibits cell migration and clonogenic survival, induces apoptosis through nuclear condensation, and increases reactive oxygen species (ROS), indicating oxidative stress as its cytotoxic mechanism.

PMID:
42852770
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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