title: Novel indolin-2-one-based sulfonamides as carbonic anhydrase inhibitors: Synthesis, in vitro biological evaluation against carbonic anhydrases isoforms I, II, IV and VII and molecular docking studies.
abstract: Herein we present the design, synthesis, and biological evaluation of three different series of novel sulfonamides (3a-f, 6a-f and 9a-f) incorporating substituted indolin-2-one moieties (as tails) linked to benzenesulfonamide (as zinc anchoring moieties) through aminoethyl or (4-oxothiazolidin-2-ylidene)aminoethyl linkers. The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IV and VII. All these isoforms were inhibited by the sulfonamides reported here in variable degrees. hCA I was inhibited with KIs in the range of 42-8550.9 nM, hCA II in the range of 5.9-761 nM; hCA IV in the range of 4.0-2069.5 nM, whereas hCA VII in the range of 13.2-694 nM. Molecular docking studies were carried out for some of the tested compounds within the hCA II active site, allowed us to rationalize the obtained inhibition results.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt. Electronic address: wagdy2000@gmail.com.
authors.forename: Wagdy M
authors.initials: WM
authors.lastname: Eldehna
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Abbassia, P.O. Box 11566, Egypt.
authors.forename: Ghada H
authors.initials: GH
authors.lastname: Al-Ansary
authors.affiliation: Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino (Firenze), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bua
authors.affiliation: Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino (Firenze), Italy; 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.
authors.forename: Alessio
authors.initials: A
authors.lastname: Nocentini
authors.affiliation: 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.
authors.forename: Paola
authors.initials: P
authors.lastname: Gratteri
authors.affiliation: Industrial Biotechnology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Egypt.
authors.forename: Ayman
authors.initials: A
authors.lastname: Altoukhy
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Hazem
authors.initials: H
authors.lastname: Ghabbour
authors.affiliation: The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt.
authors.forename: Hanaa Y
authors.initials: HY
authors.lastname: Ahmed
authors.affiliation: Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors; D030741:Carbonic Anhydrase IV / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007211:Indoles; D007527:Isoenzymes; D013449:Sulfonamides; C456900:indolin-2-one; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D030741:Carbonic Anhydrase IV; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI
keywords: 4-(2-Aminoethyl)benzenesulfonamide; Carbonic anhydrase; Isatin; Synthesis