Thiazole-substituted benzenesulfonamides as inhibitors of 12 human carbonic anhydrases |
| |
| Institution: | 1. Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Saulėtekio al. 7, Vilnius LT-10257, Lithuania;2. Department of Organic Chemistry, Faculty of Chemistry and Geosciences, Vilnius University, Naugarduko 24, Vilnius LT-03225, Lithuania;1. Department of Chemistry, Quaid-i-Azam University, 45320, Islamabad, Pakistan;2. Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Adiyaman University, 02040 Adiyaman, Turkey;2. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy;3. Department of Pharmacology, Faculty of Pharmacy, Adiyaman University, 02040 Adiyaman, Turkey;1. Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan;2. Università degli Studi di Firenze, Department NEUROFARBA – Pharmaceutical and Nutraceutical Section, University of Firenze, via Ugo Schiff 6, I-50019 Sesto Fiorentino, Firenze, Italy;3. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy;1. Technical Sciences Vocational School, Giresun University, 28049 Giresun, Turkey;2. Ağrı İbrahim Çeçen University, Department of Pharmaceutical Technology, 04100 Ağrı, Turkey;3. Ağrı İbrahim Çeçen University, Science and Art Faculty, Chemistry Department, 04100 Ağrı, Turkey;4. Universitá degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze, Polo Scientifico, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;1. Saint Petersburg State University, Saint Petersburg 199034, Russian Federation;2. Department of Organic Chemistry, Faculty of Science, RUDN University, 117198, Russian Federation;3. The Ushinsky Yaroslavl State Pedagogical University, Yaroslavl 150000, Russian Federation;4. Department of Pharmacy, University of Pisa, 56126 Pisa, Italy;5. Neurofarba Department, Universita degli Studi di Firenze, Florence, Italy;1. Department of Chemistry, Jamia Millia Islamia, New Delhi 110025, India;2. Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India |
| |
| Abstract: | Four series of para or meta - substituted thiazolylbenzenesulfonamides bearing Cl substituents were designed, synthesized, and evaluated as inhibitors of all 12 catalytically active recombinant human carbonic anhydrase (CA) isoforms. Observed affinities were determined by the fluorescent thermal shift assay and the intrinsic affinities were calculated based on the fractions of binding-ready deprotonated sulfonamide and CA bearing protonated hydroxide bound to the catalytic Zn(II) in the active site. Several compounds exhibited selectivity towards CA IX, an anticancer target. Intrinsic affinities reached 30 pM, while the observed affinities - 70 nM. The structure-intrinsic affinity relationship map of the compounds showed the energetic contributions of the thiazole ring and its substituents. |
| |
| Keywords: | Thiazole Fluorescent thermal shift assay ThermoFluor® Sulfonamide |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
