title: Substituted benzene sulfonamides incorporating 1,3,5-triazinyl moieties potently inhibit human carbonic anhydrases II, IX and XII.
abstract: A series of benzene sulfonamides incorporating 1,3,5-triazinyl moieties were synthesized using cyanuric chloride as starting material. Inhibition studies against human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) isoforms were performed with the new compounds. hCA I was modestly inhibited (KIs in the range of 87 nM-4.35 μM), hCA II was moderately inhibited by most of the new compounds (KIs in the range of 12.5-130 nM), whereas the tumor associated isoforms were potently inhibited, with KIs in the range of 1.2-34.1 nM against hCA IX and of 2.1-33.9 against hCA XII, respectively. Docking studies of some of the new compounds showed an effective binding mode within the enzyme active site, as demonstrated earlier by X-ray crystallography for structurally-related sulfonamides incorporating 1,3,5-triazinyl functionalities.
authors: Shri G.S. Institute of Technology and Science, Department of Pharmacy, 23, Park Road, Indore 452003, Madhya Pradesh, India.
authors: Amrita K
authors: AK
authors: Saluja
authors: Shri G.S. Institute of Technology and Science, Department of Pharmacy, 23, Park Road, Indore 452003, Madhya Pradesh, India. Electronic address: mtiwari@sgsits.ac.in.
authors: Meena
authors: M
authors: Tiwari
authors: Università degli Studi di Firenze, Dipartimento di Chimica, Lab. Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, I-50019 Sesto Fiorentino (Florence), Italy.
authors: Daniela
authors: D
authors: Vullo
authors: Università degli Studi di Firenze, Dipartimento di Chimica, Lab. Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, I-50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000378:metabolism; D001554:Benzene / Q000737:chemistry; D001665:Binding Sites; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014227:Triazines / Q000737:chemistry*
chemical_list: D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D014227:Triazines; D024402:Carbonic Anhydrase II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII; D001554:Benzene
keywords: 1,3,5-Triazine; Benzene sulfonamides; Carbonic anhydrase; Enzyme inhibition; Isoform selectivity; Molecular docking