title: New aminobenzenesulfonamide-thiourea conjugates: synthesis and carbonic anhydrase inhibition and docking studies.
abstract: A variety of 1-substituted-3-(3-aminosulfonylphenyl)thioureas (3a-k) and two new 1-aroyl-3-(4-aminosulfonylphenyl)thiourea derivatives (5a and 5b) were synthesized by reaction of 3-aminobenzenesulfonamide and 4-aminobenzenesulfonamide respectively with freshly prepared aroyl/heteroaryl isothiocyanates in dry acetonitrile. FTIR, (1)H NMR, (13)C NMR, GC-MS and elemental analyses data confirmed the assigned structures to the synthesized compounds. Further structure of compound (3g) was also confirmed by single crystal XRD analysis. The compounds were investigated as inhibitors of the bovine erythrocyte carbonic anhydrase isoform II (bCA II). The inhibition constants of these compounds against bCA II were in the range 0.011-17.1 μM. Among the evaluated compounds, 1-substituted -3-(3-aminosulfonylphenyl)thiourea derivatives 3h and 5a were the most potent inhibitors with IC50 of 0.052 and 0.011 μM, respectively. In silico docking and molecular dynamics simulation studies were performed against bCA II and human CA II enzymes to rationalize the inhibitory properties of these compounds.
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Sumera
authors.initials: S
authors.lastname: Zaib
authors.affiliation: Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan. Electronic address: aamersaeed@yahoo.com.
authors.forename: Aamer
authors.initials: A
authors.lastname: Saeed
authors.affiliation: Department Chemie, Fakultät für Naturwissenschaften, Universität Paderborn, Warburgerstrasse 100, D-33098 Paderborn, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Stolte
authors.affiliation: Department Chemie, Fakultät für Naturwissenschaften, Universität Paderborn, Warburgerstrasse 100, D-33098 Paderborn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Flörke
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute SCAI, Sankt Augustin, Germany.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan; Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013424:Sulfanilamides / Q000737:chemistry / Q000494:pharmacology*; D013890:Thiourea / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013424:Sulfanilamides; D002256:Carbonic Anhydrases; D013890:Thiourea
keywords: 1-Aroyl/heteroaryl-3-(3-aminosulfonylphenyl)thioureas; 3-Aminobenzenesulfonamide; Carbonic anhydrase; Molecular dynamics simulation