title: Carbonic anhydrase inhibitors. Inhibition of the cytosolic and tumor-associated carbonic anhydrase isozymes I, II and IX with some 1,3,4-oxadiazole- and 1,2,4-triazole-thiols.
abstract: Novel mercapto-1,3,4-oxadiazole and -1,2,4-triazole derivatives were synthesized by various pathways starting from 4-(4-halogeno-phenylsulfonyl)benzoic acid hydrazides which were reacted with carbon disulfide or isothiocyanates. The heterocyclic mercaptans prepared in this way were assayed as inhibitors of three physiologically relevant isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), i.e., the cytosolic CA I and II, and the tumor-associated, transmembrane isozyme CA IX. Interesting biological activity was detected for some of the new mercaptans, with inhibition constants in the low micromolar range.
authors.affiliation: Organic Chemistry Department, Faculty of Pharmacy, Traian Vuia Street 6, 020956 Bucharest, Romania.
authors.forename: Gabriela Laura
authors.initials: GL
authors.lastname: Almajan
authors.forename: Stefania-Felicia
authors.initials: SF
authors.lastname: Barbuceanu
authors.forename: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D024401:Carbonic Anhydrase I / Q000378:metabolism*; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D024403:Carbonic Anhydrase III / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D010069:Oxadiazoles; D013438:Sulfhydryl Compounds; D014230:Triazoles; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D024403:Carbonic Anhydrase III