Synthesis,molecular docking analysis and carbonic anhydrase I-II inhibitory evaluation of new sulfonamide derivatives |
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| Institution: | 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eski?ehir, Turkey;2. Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eski?ehir, Turkey;3. Department of Pharmacy Services, Nihat Delibalta Göle Vocational High School, Ardahan University, 75700 Ardahan, Turkey;4. Department of Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eski?ehir, Turkey;5. Open Education Faculty, Anadolu University, 26470 Eski?ehir, Turkey;6. Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eski?ehir, Turkey;1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;2. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;3. Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj, Saudi Arabia;4. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;1. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia;2. Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia;3. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;4. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;1. Department of Biology, Faculty of Science, Razi University, 67149-67346 Kermanshah, Iran;2. Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, and Medical Biology Research Center, Kermanshah University of Medical Sciences, 67145-1673 Kermanshah, Iran;1. School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China;2. State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, China;3. Chongqing Key Laboratory of Targeted Drug Screening and Activity Evaluation, Chongqing, 400054, China;4. Chongqing Key Laboratory of Medicinal Chemistry and Molecular Pharmacology, Chongqing, 400054, China;1. Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835215, India;2. Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy;3. Università degli Studi di Firenze, NEUROFARBA Department, Section of Pharmaceutical Chemistry, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy;1. Pharmacognosy Department, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia;2. Drug Radiation Research Department, National Center for Radiation Research & Technology, Atomic Energy Authority, Cairo, Egypt;3. Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy;4. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Al-Aini st., PO Box 11562, Cairo, Egypt;5. Università degli Studi di Firenze, Polo Scientifico, Dipartimento Neurofaba; Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy |
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| Abstract: | New sulfonamide-hydrazone derivatives (3a-3n) were synthesized to evaluate their inhibitory effects on purified human carbonic anhydrase (hCA) I and II. The inhibition profiles of the synthesized compounds on hCA I-II isoenzyme were investigated by comparing their IC50 and Ki values. Acetazolamide (5-acetamido-1,3,4-thiadiazole-2-sulfonamide, AZA) has also been used as a standard inhibitor. The compound 3e demonstrated the best hCA I inhibitory effect with a Ki value of 0.1676 ± 0.017 µM. Besides, the compound 3m showed the best hCA II inhibitory effect with a Ki value of 0.2880 ± 0.080 µM. Cytotoxicity of the compounds 3e and 3m toward NIH/3T3 mouse embryonic fibroblast cell line was observed and the compounds were found to be non-cytotoxic. Molecular docking studies were performed to investigate the interaction types between active compounds and hCA enzymes. Pharmacokinetic profiles of compounds were assessed by theoretical ADME predictions. As a result of this study a novel and potent class of CA inhibitors were identified with a good activity potential. |
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| Keywords: | Carbonic anhydrase Sulfonamide Cytotoxicity Molecular docking ADME |
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