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.
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.
Almajan
Gabriela Laura
GL
Organic Chemistry Department, Faculty of Pharmacy, Traian Vuia Street 6, 020956 Bucharest, Romania.
Barbuceanu
Stefania-Felicia
SF
Innocenti
Alessio
A
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
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*
D002257:Carbonic Anhydrase Inhibitors; D010069:Oxadiazoles; D013438:Sulfhydryl Compounds; D014230:Triazoles; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D024403:Carbonic Anhydrase III