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 muM. 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 HE staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.
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State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.;