Diaryl-substituted benzimidazole derivatives as antiproliferative agents: Design, synthesis, in vitro activity, and SAR analysis


GÜRSOY Ş., Ersan R. H.

Journal of Molecular Structure, cilt.1308, 2024 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1308
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.molstruc.2024.137960
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: Antiproliferative activity, Benzimidazoles, Cytotoxicity, Molecular docking, Synthesis
  • Erzincan Binali Yıldırım Üniversitesi Adresli: Evet

Özet

In this study, a series of 1,2-disubstituted benzimidazoles, designed to mimic nucleotides and interact favorably with amino acids in protein active sites, were synthesized and characterized. These compounds were characterized using IR, NMR spectral data, and elemental analyses, leveraging the recognition of substituted benzimidazoles as pharmacophores in the literature due to their documented anticancer activities. The compounds involved chloro and substituted phenyl rings, known for their anticancer activities, as key pharmacophores. Cytotoxicity assessments using the MTT assay were performed against MCF7, MDA-MB-231, and normal mouse fibroblasts (L929) for all synthesized compounds (11–19). Among them, compound 13 exhibited the most significant activity, inducing cell cycle arrest at the G0/G1 phase in MCF7 cells, suggesting its potential as an antitumor agent through apoptosis. To understand the underlying mechanisms of apoptotic cell death induced by compound 13, we investigated the involvement of apoptotic proteins such as Bax, Bcl-2, and p53. Our findings highlight Compound 13 as a promising scaffold for further optimization in the development of effective anticancer drugs.