Bovine carbonic anhydrase (bCA) inhibitors: Synthesis, molecular docking and theoretical studies of bisoxadiazole-substituted sulfonamide derivatives

Eybek A., Kaya M. O., Güleç Ö., Demirci T., Musatat A. B., Özdemir O., ...Daha Fazla

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, cilt.267, ss.131489, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 267
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.ijbiomac.2024.131489
  • Dergi Adı: INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, INSPEC, Veterinary Science Database
  • Sayfa Sayıları: ss.131489
  • Kocaeli Üniversitesi Adresli: Evet

Özet

This paper describes the in vitro inhibition potential of bisoxadiazole-substituted sulfonamide derivatives (6a-t) against bovine carbonic anhydrase (bCA) after they were designed through computational analyses and evalu- ated the predicted interaction via molecular docking. First, in silico ADMET predictions and physicochemical property analysis of the compounds provided insights into solubility and permeability, then density functional theory (DFT) calculations were performed to analyse their ionization energies, nucleophilicity, in vitro electron affinity, dipole moments and molecular interactions under vacuum and dimethyl sulfoxide (DMSO) conditions. After calculating the theoretical inhibition constants, IC50 values determined from enzymatic inhibition were found between 12.93 and 45.77 μM. Molecular docking evaluation revealed favorable hydrogen bonding and π-interactions of the compounds within the bCA active site. The experimentally most active compound, 6p, exhibited the strongest inhibitory activity with a theoretical inhibition constant value of 9.41 nM and H-bonds with Gln91, Thr198, and Trp4 residues and His63 Pi-cation interactions with His63 residues. Overall, the study reveals promising bCA blocking potential for the synthesized derivatives, similar to acetazolamide.