ABSTRACT
Secondary sulfonamides (4a-8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives (4a-8h) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives (4a-8h) are effective LPO inhibitors. The Ki values of secondary sulfonamide derivatives (4a-8h) were found in the range of 1.096 × 10-3 to 1203.83 µM against LPO. However, the most effective inhibition was found for N-(sulfathiazole)-3,4,5-triacetoxybenzamide (6a), with Ki values of 1.096 × 10-3 ± 0.471 × 10-3 µM as non-competitive inhibition.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Lactoperoxidase/antagonists & inhibitors , Lactoperoxidase/metabolism , Sulfonamides/chemistry , Sulfonamides/pharmacology , Isoxazoles/chemistry , Pyridines/chemistry , Pyrimidines/chemistry , Thiadiazoles/chemistryABSTRACT
Four groups of novel sulfonamide derivatives: (i) acetoxybenzamide, (ii) triacetoxybenzamide, (iii) hydroxybenzamide and (iv) trihydroxybenzamide, all having thiazole, pyrimidine, pyridine, isoxazole and thiadiazole moieties were prepared and their inhibitory effects were studied on two metalloenzymes, i.e. carbonic anhydrase isozymes (hCA I and II), purified from human erythrocyte cells by Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. These enzymes are present in almost all living organisms to catalyse the synthesis of bicarbonate ion (HCO3-) from carbon dioxide and water. The sulfonamide derivatives were found to be active against hCA I and II in the range of 2.62-136.54 and 5.74-210.58 nM, respectively.
