title: Carbonic anhydrase inhibitors. Benzenesulfonamides incorporating cyanoacrylamide moieties strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase.
abstract: A series of benzenesulfonamides incorporating cyanoacrylamide moieties (tyrphostine analogs) were assayed as inhibitors of the β-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA. Some of these compounds were low nanomolar or subnanomolar ScCA inhibitors and showed selectivity ratios in the range of 4.91-69.86 for inhibiting the yeast enzyme over the offtarget human (h) isoforms hCA I and of 6.46-13.52 for inhibiting ScCA over hCA II. The model organism S. cerevisiae and this particular enzyme may be useful for detecting antifungals with a novel mechanism of action compared to the classical azole drugs to which significant drug resistance emerged. Indeed, some of these sulfonamides inhibited the growth of the yeast with CC50-s in the range of 0.73-6.54 μM.
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, PO Box 173, Alkharj 11942, Saudi Arabia. alafeefy@hotmail.com
authors: Ahmed M
authors: AM
authors: Alafeefy
authors: Semra
authors: S
authors: Isik
authors: Nabila A
authors: NA
authors: Al-Jaber
authors: Daniela
authors: D
authors: Vullo
authors: Hatem A
authors: HA
authors: Abdel-Aziz
authors: Abdelkader E
authors: AE
authors: Ashour
authors: Amani S
authors: AS
authors: Awaad
authors: Clemente
authors: C
authors: Capasso
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D000935:Antifungal Agents; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D000096926:Benzenesulfonamides