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


Ilhan S., Camli Pulat C., Oguz F., BEKTAŞ H., MENTEŞE E., ATMACA H.

MOLECULAR DIVERSITY, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1007/s11030-022-10524-3
  • Journal Name: MOLECULAR DIVERSITY
  • Journal Indexes: Science Citation Index Expanded, Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: Benzimidazole derivatives, Anticancer drugs, Apoptosis, Bcl-2, IN-VITRO, ANTICANCER

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 mu g/mL. Among all derivatives, compounds C1 and D1 demonstrated a higher cytotoxic effect on cancer cells with IC50 values < 50 mu g/mL, while a lower cytotoxic effect against human embryonic kidney cells with IC50 values of > 100 mu g/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.