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, cilt.27, sa.4, ss.1703-1712, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 4
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s11030-022-10524-3
  • Dergi Adı: MOLECULAR DIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1703-1712
  • Anahtar Kelimeler: Benzimidazole derivatives, Anticancer drugs, Apoptosis, Bcl-2, IN-VITRO, ANTICANCER
  • Recep Tayyip Erdoğan Üniversitesi Adresli: Evet

Özet

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.