Synthesis,biological evaluation and computational studies of novel iminothiazolidinone benzenesulfonamides as potent carbonic anhydrase II and IX inhibitors |
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| Affiliation: | 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. 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, Hafiz Hayat Campus, University of Gujrat, Gujrat, Pakistan;2. National Medicines Institute, Chełmska 30/34, 00-725, Warsaw, Poland;3. National Centre for Nuclear Research, Andrzeja Sołtana 7, 05-400, Otwock, Poland;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum 25240, Turkey;2. Meikai University Research Institute of Odontology (M-RIO), Sakado, Saitama 350-0283, Japan;3. Neurofarba Department, Sezione di Scienza Farmaceutiche e Nutraceutiche, Universita degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy;4. Latvian Biomedical Research and Study Center, Ratsupites 1, Riga, Latvia;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri 04100, Turkey;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 Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;2. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;3. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;4. Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt;3. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy;4. 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;5. Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt;6. School of Chemistry, University of Wollongong, Wollongong, 2522, New South Wales, Australia;7. Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, Egypt;8. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia;9. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt;10. The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt;11. Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo, 12622, Egypt |
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| Abstract: | A series of iminothiazolidinone-sulfonamide hybrids (2a-k) was synthesized by heterocyclization of sulfanilamide thioureas with methyl bromoacetate and characterized by spectroscopic techniques, mass and elemental analysis. The synthesized derivatives were screened against four relevant human (h) isoforms of carbonic anydrases (CAs, EC 4.2.1.1) I, II, IV and IX. These enzymes are involved in a variety of diseases, including glaucoma, retinitis pigmentosa, epilepsy, arthritis, and tumors. Derivatives 2a-2k exhibited the best inhibitory activity against the cytosolyc hCA II (KIs are reaching the sub-nanomolar range, 0.41–37.8 nM) and against the tumor-associated isoform hCA IX (KIs are spanning between 24.3 and 368.3 nM). The binding mode of the reported iminothiazolidinone benzenesulfonamides within hCA II and IX catalytic clefts was investigated by docking studies. |
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| Keywords: | Carbonic anhydrase Zinc-binding group Nanomolar inhibition Anti-glaucoma Anti-tumour |
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