title: Synthesis and biological activity of novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease.
abstract: Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 3o, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Shilin
authors.initials: S
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.forename: Jinying
authors.initials: J
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Xia
authors.initials: X
authors.lastname: Ye
authors.forename: Zhizhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Jincheng
authors.initials: J
authors.lastname: Yang
authors.forename: Neng
authors.initials: N
authors.lastname: Qiu
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Wang
authors.forename: Aihua
authors.initials: A
authors.lastname: Peng
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D052242:Adiponectin / Q000096:biosynthesis; D000818:Animals; D001463:Barbiturates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy*; D020738:Leptin / Q000096:biosynthesis; D008297:Male; D051379:Mice; D015394:Molecular Structure; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013858:Thiobarbiturates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D001463:Barbiturates; D020738:Leptin; D013858:Thiobarbiturates; C029684:thiobarbituric acid; C032232:barbituric acid