Crystal Structure–Activity Relationship of Some MeOPhenylacrylonitriles: Dual Antimicrobial–Cytotoxic Effectsand in Silico Perspectives

Babali Özen L., Ekici Ö., Özen F., Berberler S., Özkan G., Yılmaz Öztürk B., ...Daha Fazla

CHEMISTRYOPEN, cilt.15, sa.7, ss.1-10, 2025 (SCI-Expanded)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 7
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/open.202500280
  • Dergi Adı: CHEMISTRYOPEN
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, EMBASE, MEDLINE, Directory of Open Access Journals
  • Sayfa Sayıları: ss.1-10
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Herein, methoxy-substituted phenylacrylonitrile derivatives 2(a–c)are synthesized via Knoevenagel condensation and characterizedusing fourier-transform infrared spectroscopy, nuclear magneticresonance spectroscopy, and X-ray crystallography (for 2a and2b). Although compounds 2a and 2b have previously beenreported in terms of their structural features, their dual antimicro-bial and anticancer activities, as well as crystallographic structure–activity relationships, have not yet been investigated. Notably, noearlier studies assessed their selective cytotoxicity using bothcancerous (MCF-7) and healthy (L929) cell lines—a gap addressedin this work. Molecular docking analyzes reveal strong bindingaffinities to biological targets, including penicillin binding protein2 (PBP2) (8.4 kcal mol1 for 2c) and CDK1/Cks2 (9.5 kcal mol1for 2c), highlighting their dual-action potential. Antimicrobialassays against nine bacterial strains show minimum inhibitoryconcentration values ranging from 2.5 to 25 mg mL1, with 2cexhibiting notable activity against gram-positive bacteria.Cytotoxicity assays demonstrate potent effects against MCF-7 cells(IC50: 34 μM for 2b, 44 μM for 2a), while 2c shows broader but mod-erate activity. The integration of crystallographic, docking, and bio-logical assays underscores the therapeutic potential of thesederivatives, with 2(a,b) emerging as selective candidates for breastcancer treatment