Carbonic anhydrase inhibitors: Synthesis,molecular docking,cytotoxic and inhibition of the human carbonic anhydrase isoforms I,II, IX,XII with novel benzenesulfonamides incorporating pyrrole,pyrrolopyrimidine and fused pyrrolopyrimidine moieties |
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| Affiliation: | 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;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. Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;2. Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan;3. Department Chemie, Fakultät für Naturwissenschaften, Universität Paderborn, Warburgerstrasse 100, D-33098 Paderborn, Germany;4. Department of Bioinformatics, Fraunhofer Institute SCAI, Sankt Augustin, Germany;5. Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;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. Faculty of Science, Department of Chemistry, Atatürk University, 25240 Erzurum, Turkey;2. Gumushane University, Vocational School of Health Services, Department of Medical Services and Techniques, Gumushane, Turkey;3. Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia;4. Università degli Studi di Firenze, Neurofarba Department, Rm. 66, via U. Schiff 6, I-50019 Sesto Fiorentino (Firenze), Italy;1. University of Florence, Department of Chemistry "Ugo Schiff", Via della Lastruccia 3-13, I-50019, Sesto Fiorentino, Italy;2. NEUROFARBA Department, Section of Pharmacology and Toxicology, Università degli Studi di Firenze, Viale Pieraccini 6, 50139, Florence, Italy;3. CSIRO, 343 Royal Parade, Parkville, Victoria, 3052, Australia;4. Department of University of Florence, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Florence, Italy;5. Centre of Advanced Research in Bionanoconjugates and Biopolymers Department, “Petru Poni” Institute of Macromolecular Chemistry, Iasi, Romania |
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| Abstract: | A series of novel pyrroles, pyrrolopyrimidines, pyrazolopyrrolopyrimidine, triazolopyrrolopyrimidines, tetrazolopyrrolopyrimidine, triazinopyrrolopyrimidines and pyrrolopyrimidotriazepines bearing the biologically active benzenesulfonamide moiety were synthesized by using pyrrole-o-amino-carbonitrile as key intermediate. All the synthesized compounds were evaluated for their in vitro carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects against the human (h) isoforms hCA I, II, IX and XII. Among the tested derivatives, compounds 16, 18 and 20–24 showed potent activity as inhibitors for the tumor associated transmembrane isoforms (hCA IX and XII) in the nanomolar and subnanomolar range, with high selectivity. All compounds underwent cytotoxic activity assays on human breast cancer cell line (MCF-7) showing effective activity, comparable to that of the clinically used drug doxorubicin. |
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| Keywords: | Pyrrolopyrimidines Sulfonamide Cytotoxic activity Carbonic anhydrase inhibitors Molecular docking |
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