Design and synthesis of benzimidazole derivatives as apoptosis-inducing agents by targeting Bcl-2 protein

Mol Divers. 2023 Aug;27(4):1703-1712. doi: 10.1007/s11030-022-10524-3. Epub 2022 Sep 5.

Abstract

Bcl-2, an anti-apoptotic protein, is a well-known and appealing cancer therapy target. Novel series of benzimidazole derivatives were synthesized and tested for their activity as Bcl-2 inhibitors on T98G glioblastoma, PC3 prostate, MCF-7 breast, and H69AR lung cancer cells. MTT assay was used to evaluate the cytotoxic effect. PI Annexin V Apoptosis Detection Kit was used to detect apoptosis. Expression levels of the Bcl-2 protein were examined by the Western blot analysis and qRT-PCR. All synthesized benzimidazole derivatives exhibited a cytotoxic effect on cancer cells with IC50 values in the range of 25.2-88.2 µg/mL. Among all derivatives, compounds C1 and D1 demonstrated a higher cytotoxic effect on cancer cells with IC50 values < 50 µg/mL, while a lower cytotoxic effect against human embryonic kidney cells with IC50 values of > 100 µg/mL. C1 and D1 caused a significant increase in the percentage of apoptotic cells in all types of cancer cell cells and both Bcl-2 mRNA and protein levels were significantly reduced. These results suggest that the novel benzimidazole derivatives may be candidates for apoptosis-inducing agents in cancer treatment by targeting anti-Bcl-2 proteins in cancer cells.

Keywords: Anticancer drugs; Apoptosis; Bcl-2; Benzimidazole derivatives.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Benzimidazoles / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans

Substances

  • Antineoplastic Agents
  • Benzimidazoles