Sulfa Drugs as Inhibitors of Carbonic Anhydrase: New Targets for the Old Drugs

• Published in: BioMed research international 2014-01, Vol.2014 (2014), p.1-10
• Main Authors: Altaf, Aisha, Hamayoun, Mehwish, Hussain, Sajad, al-Rashida, Mariya, Iqbal, Jamshed
• Format: Article
• Language: English
• Subjects: Animals; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrases - biosynthesis; Carbonic Anhydrases - drug effects; Cattle; Dosage and administration; Drug targeting; Drugs; Enzymes; Forecasts and trends; Health aspects; Hydrogen bonds; Molecular weight; Protein folding; Sulfadiazine - analogs & derivatives; Sulfadiazine - chemical synthesis; Sulfadiazine - pharmacology; Sulfamerazine - analogs & derivatives; Sulfamerazine - chemical synthesis; Sulfamerazine - pharmacology; Sulfamethazine - analogs & derivatives; Sulfamethazine - chemical synthesis; Sulfamethazine - pharmacology; Sulfaquinoxaline - analogs & derivatives; Sulfaquinoxaline - chemical synthesis; Sulfaquinoxaline - pharmacology; Sulfonamides
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/162928

Sulfa drugs are well-known antibacterial agents containing N-substituted sulfonamide group on para position of aniline ring (NH2RSO2NHR′). In this study 2,4-dichloro-1,3,5-triazine derivatives of sulfa drugs, sulfamerazine (1b), sulfaquinoxaline (2b), sulfadiazine (3b), sulfadimidine (4b), and sulfachloropyrazine (5b) (1a–5a) were synthesized and characterized. Their carbonic anhydrase inhibition activity was evaluated against bovine cytosolic carbonic anhydrase isozyme II (bCA II). For the sake of comparison the CA inhibition activity of the parent sulfa drugs (1b–5b) was also evaluated. A significant increase in CA inhibition activity of sulfa drugs was observed upon substitution with 2,4-dichloro-1,3,5-triazine moiety. Molecular docking studies were carried out to highlight binding site interactions. ADME properties were calculated to evaluate drug likeness of the compounds.