Sulfonamides linked to sulfonate esters via hydrazone functionality: synthesis, human carbonic anhydrase inhibitory activities, and molecular modeling studies
New Journal of Chemistry, cilt.47, sa.9, ss.4267-4276, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 47 Sayı: 9
- Basım Tarihi: 2023
- Doi Numarası: 10.1039/d2nj05703d
- Dergi Adı: New Journal of Chemistry
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, DIALNET
- Sayfa Sayıları: ss.4267-4276
- Hacettepe Üniversitesi Adresli: Evet
Özet
© 2023 The Royal Society of Chemistry.In the present study, we synthesized novel carbonic anhydrase (CA, EC 4.2.1.1) inhibitors by linking various sulfonate esters to a benzenesulfonamide fragment via hydrazone functionality (SH1-SH14). Following structural characterization using spectral techniques, the obtained molecules were screened for their inhibitory potential against tumor-associated human (h) isoforms hCA IX and XII, along with the physiologically dominant isoforms hCA I and II. Introducing methyl, methoxy or chlorine substituents into the para position of the terminal phenyl ring led to the most effective hCA IX and/or hCA XII inhibitors, with Ki values < 10 nM. Drug-likeness and pharmacokinetic profiles of the selected compounds were predicted using in silico techniques. Finally, molecular docking studies of the most effective inhibitor, 4-((2-(4-sulfamoylbenzoyl)hydrazono)methyl)phenyl 4-methoxybenzenesulfonate (SH3), against the tumor-associated hCA isoforms IX (Ki = 9.4 nM) and XII (Ki = 5.9 nM) were carried out to rationalize the inhibition data.