Synthesis, characterization, and multi-target In silico evaluation of Cu(II) complexes derived from novel sulfisoxazole ligands: molecular docking, ADME/toxicity, and drug-likeness studies

Alyar S., Bilkan M. T., Bilkan Ç., Alyar H., ÖZDEMİR ÖZMEN Ü., Bilen Ayan E.

Journal of Coordination Chemistry, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1080/00958972.2026.2658131
  • Dergi Adı: Journal of Coordination Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica
  • Anahtar Kelimeler: ADME/Tox prediction, antibacterial activity, Copper(II) complexes, molecular docking, sulfisoxazole derivatives
  • Gazi Üniversitesi Adresli: Evet

Özet

Two distinct ferrocene-based sulfisoxazole ligands (S1M–S5 and S2M–S5) were employed to synthesize two structurally related but electronically differentiated Cu(II) complexes, Cu(S1M–S5)2 and Cu(S2M–S5)2. Both complexes were comprehensively characterized through CHN elemental analysis, FT-IR spectroscopy, LC–MS, molar conductivity measurements, and thermogravimetric analysis, all of which confirmed the successful formation of neutral ML2-type chelates featuring O,N-bidentate coordination. Their antibacterial potential was explored via in silico molecular docking against clinically relevant bacterial targets, including topoisomerase and DNA gyrase enzymes, with binding profiles benchmarked against ciprofloxacin. Both Cu(II) complexes exhibited markedly stronger binding affinities than reference antibiotic. Complementary ADME and toxicity predictions further indicated favorable drug-likeness, high predicted gastrointestinal absorption, and low acute toxicity. Altogether, the combined structural, stability, and computational findings highlight these two ligand-derived Cu(II) complexes as promising and mechanistically versatile antibacterial candidates.