Design, synthesis, and anticancer evaluation of benzimidazole and benzothiazole derivatives targeting Hsp70 and FoxM1
- Bioorg Med Chem Lett. 2025 Sep 10:130:130401. doi: 10.1016/j.bmcl.2025.130401.
- 1. School of Medicine, Arak University of Medical Sciences, Arak, Iran; School of Health, Arak University of Medical Sciences, Arak, Iran; Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
- 2. Department of Molecular, Cellular, and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY, USA; Graduate Program in Biology, City University of New York Graduate Center, New York, USA; Department of Chemistry and Physics, State University of New York at Old Westbury, New York, USA. Electronic address: [email protected].
- 3. Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
- 4. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran; Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: [email protected].
A series of novel benzimidazole and benzothiazole derivatives was designed based on the scaffolds of known HSP70 (VER-155008) and FoxM1 (FDI-6) inhibitors. Molecular docking studies indicated favorable binding affinities to both targets, with several compounds showing strong interactions within the ATPase domain of HSP70 and the DNA-binding region of FoxM1. The most promising candidates, as identified by docking scores, were synthesized and structurally confirmed using FT-IR, 1H NMR, and 13C NMR spectroscopy. Their cytotoxicity was evaluated against MCF-7, HeLa, and HUVEC cell lines using the MTT assay. Benzothiazole derivatives exhibited greater cytotoxic activity than benzimidazole counterparts. Among them, compound 7d demonstrated the most potent antiproliferative effect, with IC₅₀ values of 10.83 μM (MCF-7), 12.68 μM (HeLa), and 106.75 μM (HUVEC). Molecular dynamics simulations further confirmed the stability of 7d within the FoxM1 binding pocket, supporting its role as a potential FoxM1 inhibitor. While experimental confirmation of dual-target inhibition in cell-based assays is pending, the computational findings suggest that 7d may function as a dual modulator of HSP70 and FoxM1, warranting further mechanistic investigation.
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Cat. No.Product NameDescriptionTargetResearch Area
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Research Areas: Cancer