Design, Synthesis, Cytotoxic Evaluation, and Multilevel Computational Studies of Novel Benzofuran-3-one Hybrids Bearing 1,2,3-Triazole and Pyrazole Scaffolds against AGS and MCF-7 Cancer Cells
JOURNAL OF MOLECULAR STRUCTURE, cilt.1377, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1377
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.molstruc.2026.147150
- Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Kocaeli Üniversitesi Adresli: Evet
Özet
As part of our ongoing efforts to develop novel anticancer agents, two series of hybrid heterocycles 12(a-j) and 13(a-j) comprising twenty novel benzofuran-3-one hybrids bearing 1,2,3-triazole and pyrazole scaffolds were designed and synthesized using click chemistry. Computational investigations, including DFT calculations, molecular docking, molecular dynamics simulations, and MM-PBSA binding free energy analysis, indicated strong binding affinity toward HER2, VEGFR2, CDK4, and CDK6 targets, indicating strong anticancer potential of these compounds. The synthesized compounds were then evaluated in vitro for their cytotoxic activity against MCF-7 and AGS cancer cell lines and exhibited low to moderate micromolar IC 50 values. Notably, compounds, 12d, 12e, 12f, 13c, 13e, and 13f demonstrated up to 25-fold greater potency than Oxaliplatin (IC 50 = 29.8 & micro;M) and Leucovorin (IC 50 =30.8 & micro;M) against AGS cancer cell line, while exhibiting negligible cytotoxicity toward the noncancerous HEK 293 cell line. Similarly, compounds 12b, 12e, and 12f, showed up to 16-fold higher potency than Paclitaxel (IC 50 = 18.5 & micro;M) against MCF-7 cancer cell line. SAR analysis revealed that electron-donating substituents enhanced cytotoxic potency, against MCF-7 cells. Overall, the hybrids showed superior anticancer potential, particularly against AGS cells, and the combined experimental and computational findings strongly support further in-depth biological evaluation and lead optimization.