title: New anti-inflammatory thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles with antioxidant properties as potential iNOS inhibitors.
abstract: The objective of this study was to investigate the anti-inflammatory and antioxidant activity of new thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azole derivatives as potential iNOS inhibitors. The in vivo anti-inflammatory effects of the new thiazole compounds were studied in a turpentine oil induced inflammation model. Their anti-inflammatory activity was assessed by evaluating the acute phase bone marrow response, phagocytes' activity, NO synthesis and antioxidant capacity. The new thiazole compounds have anti-inflammatory effects by lowering bone marrow acute phase response and oxidative stress. The best anti-inflammatory and antioxidant effect was found for thiazolyl-carbonyl-thiosemicarbazides Th-1-8, thiazolyl-1,3,4-oxadiazole Th-20 and thiazolyl-1,3,4-thiadiazole Th-21. Virtual screening of thiazole derivatives against the oxygenase domain of chain A from 2Y37 revealed that all twenty-two compounds bind the active site of inducible nitric oxide synthase (iNOS). Based on the virtual screening and on the results obtained above, the activity may be due to their capacity to reduce the NO synthesis by blocking the bind of L-Arg in the active site of iNOS, the compounds binding the synthase by hydrogen bonds between the NH (2 and/or 4) of thiosemicarbazide fragment (Th-2-8) or N2/N3 from azole cycles and by the thiol function (Th-9-22).
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Iuliu Haţieganu University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania. brandu32@yahoo.com
authors.forename: Brînduşa
authors.initials: B
authors.lastname: Tiperciuc
authors.forename: Alina
authors.initials: A
authors.lastname: Pârvu
authors.forename: Radu
authors.initials: R
authors.lastname: Tamaian
authors.forename: Cristina
authors.initials: C
authors.lastname: Nastasă
authors.forename: Ioana
authors.initials: I
authors.lastname: Ionuţ
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Oniga
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001393:Azoles / Q000138:chemical synthesis / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006860:Hydrogen Bonding; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001393:Azoles; D004791:Enzyme Inhibitors; D012663:Semicarbazides; D009569:Nitric Oxide; C005151:thiosemicarbazide; D052247:Nitric Oxide Synthase Type II