title: Novel 5-Hydroxy, 5-Substituted Benzenesulfonamide Pyrimidine-2,4,6-Triones Attenuate Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of the Gelatinases, MMP-2 and MMP-9.
abstract: Preclinical Research A novel series of ten 5-hydroxy, 5-substituted benzene sulfonamide pyrimidine-2,4,6-triones were synthesized and their structures ascertained using (1) H-NMR, (13) C-NMR, mass and elemental analysis. These compounds were subsequently tested for inhibition of MMP-2 and MMP-9 where most exhibited activity with compound 5i being the most potent against MMP-2 and MMP-9 with IC50 values of 2.35 nM and 8.24 nM, respectively. Compound 5i was further analyzed in a mouse LPS-induced acute lung injury model where it had protective activity. Histochemical studies indicated that 5i improved the vascular integrity of the lung. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Cardiothoracic Surgery, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, 210009, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Cardiothoracic Surgery, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, 210009, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, 210009, People's Republic of China.
authors.forename: Ze-Qian
authors.initials: ZQ
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, 210009, People's Republic of China.
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D018093:Gelatinases / Q000037:antagonists & inhibitors; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D018093:Gelatinases; D008070:Lipopolysaccharides; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000096926:Benzenesulfonamides
keywords: MMP-2; MMP-9; sulfonamide pyrimidine-2,4,6-triones; synthesis