Design, Synthesis, and Molecular Docking of Triazole-Coumarin Hybrids as Potent Breast Cancer Inhibitors Targeting Cell Cycle and Apoptosis

Keser M., MENTEŞE E., İLHAN M. S., EMİRİK M., ATMACA İLHAN H.

Chemistry and Biodiversity, cilt.22, sa.12, 2025 (SCI-Expanded, Scopus) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 12
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/cbdv.202501775
  • Dergi Adı: Chemistry and Biodiversity
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: apoptosis, breast cancer, cell cycle, molecular docking, triazole-coumarin hybrid
  • Manisa Celal Bayar Üniversitesi Adresli: Evet

Özet

Breast cancer continues to pose a significant global health burden, highlighting the urgent need for novel chemotherapeutic agents with improved selectivity and reduced toxicity. In this study, we rationally designed and synthesized six novel amide-bridged triazole-coumarin hybrids (5a–f) based on the known anticancer potential of both pharmacophores. The synthesized compounds were evaluated for their cytotoxicity in MCF-7 and MDA─MB─231 breast cancer cell lines and non-tumorigenic MCF-10A cells. Among them, derivative 5f showed the most potent anticancer activity with minimal toxicity toward normal cells. Mechanistic studies revealed that 5f induced apoptosis by modulating Bax and Bcl─2 expression and arrested the cell cycle at the S phase via downregulation of CDK2 and Cyclin E. Molecular docking analyses confirmed its high binding affinity to CDK2 and Bcl─2, supporting its potential as a dual-target inhibitor. These findings suggest that compound 5f is a promising lead structure for the development of selective anticancer agents targeting breast cancer.