Sulfonamides incorporating heteropolycyclic scaffolds show potent inhibitory action against carbonic anhydrase isoforms I,II, IX and XII |
| |
| Institution: | 1. Università di Pisa, Dipartimento di Farmacia, Via Bonanno 6, 56126 Pisa, Italy;2. Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy;3. Università degli Studi di Firenze, NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy;1. Imperial College Healthcare NHS Trust, London, United Kingdom;2. Imperial College London, London, United Kingdom;1. Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan;2. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;4. Center of Excellence for Advanced Materials Research (CEAMR), Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;5. Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad, Pakistan;1. Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland;2. Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy;3. Università degli Studi di Firenze, NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;4. Department of Medicinal Chemistry and Drug Technology, Medical University of Bialystok, Bialystok, Poland;5. Department of Chemistry, Laboratory of Separation and Spectroscopic Method Applications, Center for Interdisciplinary Research, The John Paul II Catholic University of Lublin, al. Krasnicka 102, 20-718 Lublin, Poland;1. Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy;2. Istituto di Biochimica delle Proteine and Institute of Bioscience and Bioresources (IBBR), CNR, Via P. Castellino 111, 80131 Napoli, Italy;3. Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia;4. Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEIROFABA, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy;1. Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India;2. Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019 Sesto Fiorentino (Firenze), Italy;3. Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy;1. Dipartimento Scienze del Farmaco e dei Prodotti per la salute, Università degli Studi di Messina, Viale Annunziata, I-98168 Messina, Italy;2. Neurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, Università degli Studi di Firenze, Sesto Fiorentino (Florence), Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;3. Institute of Molecular Genetics, ASCR, v.v.i., Vídeňská 1083, Prague 4, 14220, Czech Republic;4. Institute of Organic Chemistry and Biochemistry, ASCR, v.v.i., Flemingovo nám. 2, Prague 6, 16610, Czech Republic |
| |
| Abstract: | Three series of polycyclic compounds possessing either primary sulfonamide or carboxylic acid moieties as zinc-binding groups were investigated as inhibitors of four physiologically relevant CA isoforms, the cytosolic hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides reported here showed excellent inhibitory effects against isoforms hCA II, IX and XII, but no highly isoform-selective inhibition profiles. On the other hand, the carboxylates selectively inhibited hCA IX (KIs ranging between 40.8 and 92.7 nM) without inhibiting significantly the other isoforms. Sulfonamides/carboxylates incorporating polycyclic ring systems such as benzothiopyranopyrimidine, pyridothiopyranopyrimidine or dihydrobenzothiopyrano4,3-c]pyrazole may be considered as interesting candidates for exploring the design of isoform-selective CAIs with various pharmacologic applications. |
| |
| Keywords: | Carbonic anhydrase Sulfonamide Carboxylic acid Benzothiopyranopyrimidine Pyridothiopyranopyrimidine |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
