Synthesis, cytotoxic evaluation and molecular modeling of 5-bromo-2-methoxyphenoxy substituted phthalonitriles and phthalic acids
Journal of the Indian Chemical Society, cilt.103, sa.10, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 103 Sayı: 10
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.jics.2026.102972
- Dergi Adı: Journal of the Indian Chemical Society
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE
- Anahtar Kelimeler: Anticancer, Carboxylic acid, MTT, Nitrile, Synthesis
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
In this study, 5-bromo-2-methoxyphenol was reacted with 3- and 4-nitrophthalonitrile to synthesize phthalonitrile derivatives, which were subsequently converted into the corresponding phthalic acid derivatives The synthesized compounds were characterized by elemental analysis, FT-IR, 1H NMR and 13C NMR spectroscopy. Their cytotoxic activities were evaluated in different cell lines. In addition, the binding interactions of the compounds with vascular endothelial growth factor receptor 2 (VEGFR2) and peroxisome proliferator-activated receptor gamma (PPARγ) were investigated using molecular docking and molecular dynamics (MD) simulations. The docking results indicated that the synthesized compounds generally exhibited more favorable predicted binding toward PPARγ than VEGFR2. Among the series, compound 4 showed the highest predicted affinity for PPARγ and displayed an interaction pattern similar to that of the co-crystallized reference ligand. MD simulations supported the stability of the predicted PPARγ–compound 4 complex over the simulation period. However, MM/PBSA binding free energy calculations suggested that the reference ligand retained a stronger overall binding affinity than compound 4 . These findings identify compound 4 as a promising candidate for further biological investigation while highlighting the need for additional experimental validation.