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 & BIODIVERSITY, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/cbdv.202501775
  • Dergi Adı: CHEMISTRY & 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
  • Recep Tayyip Erdoğan 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 & horbar;MB & horbar;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 & horbar;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 & horbar;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.