title: Quinazoline-sulfonamides with potent inhibitory activity against the α-carbonic anhydrase from Vibrio cholerae.
abstract: Thirteen novel sulfonamide derivatives incorporating the quinazoline scaffold were synthesized by simple, eco-friendly procedures. These compounds were tested for their ability to inhibit the α-carbonic anhydrases (CA, EC 4.2.1.1) from Vibrio cholerae (VchCA) as well as the human α-CA isoforms, hCA I and hCA II. Nine compounds were highly effective, nanomolar inhibitors of the pathogenic enzyme VchCA. Three of them were also highly effective sub-nanomolar inhibitors of the cytosolic isoform II. The best VchCA inhibitor had a KI of 2.7 nM. Many of these developed compounds showed high selectivity for inhibition of the bacterial over the mammalian CA isoforms, with one compound possessing selectivity ratios as high as 97.9 against hCA I and 9.7 against hCA II. Compound 9d was another highly effective VchCA inhibitor presenting a selectivity ratio of 99.1 and 8.1 against hCA I and hCA II, respectively. These results suggest that sulfonamides with quinazoline backbone could be considered suitable tools to better understand the role of bacterial CAs in pathogenesis.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, PO Box 173, Alkharj 11942, Saudi Arabia. Electronic address: a.alafeefy@sau.edu.sa.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Alafeefy
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Rm 188, Via della Lastruccia 3, I 50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, PO Box 173, Alkharj 11942, Saudi Arabia.
authors.forename: Abdul-Malek S
authors.initials: AM
authors.lastname: Al-Tamimi
authors.affiliation: Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Del Prete
authors.affiliation: Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Rm 188, Via della Lastruccia 3, I 50019 Sesto Fiorentino (Firenze), Italy; Università degli Studi di Firenze, Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D011799:Quinazolines; D013449:Sulfonamides; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; Enzyme inhibitor; Quinazoline; Sulfonamide; Vibrio cholera