Synthesis, anti-diabetic evaluation and molecular docking studies of 4-(1-aryl-1H-1, 2, 3-triazol-4-yl)-1,4-dihydropyridine derivatives as novel 11-β hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitors

被引:23
|
作者
Praveenkumar, E. [1 ]
Gurrapu, Nirmala [1 ]
Kolluri, Prashanth Kumar [1 ]
Yerragunta, Vishwanadham [2 ]
Kunduru, Bharathi Reddy [3 ]
Subhashini, N. J. P. [1 ]
机构
[1] Osmania Univ, Univ Coll Sci, Dept Chem, Hyderabad 500007, Telangana, India
[2] VIPER, Bioorgan & Med Chem Res Div, Medak 502313, Telangana, India
[3] Osmania Univ, Univ Coll Sci, Dept Genet & Biotechnol, Hyderabad 500007, Telangana, India
关键词
11-BetaHydroxysteroid dehydrogenase-1(11 beta-HSD1) inhibitors 1, 4-dihydropyridine 1,2,3-Triazole; Diabetic agents and molecular docking studies; METABOLIC SYNDROME; VISCERAL OBESITY; TYPE-1; RESISTANCE;
D O I
10.1016/j.bioorg.2019.103056
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
11-Beta-Hydroxysteroid dehydrogenase-1(11 beta-HSD1) inhibitors are one of the emerging classes of molecules to fight against diabetic complications. A novel series of 4-(1-substituted-1H-1,2,3-triazol-4-yl)-1,4-dihydropyridine derivatives were synthesized and evaluated for their anti-diabetic activity. Two compounds showed antidiabetic activity very effectively. To clarify the mechanism of action of these compounds, the most potent compounds (5g and 5h) of the synthesized analogs were further studied by testing its 11-Beta Hydroxysteroid dehydrogenase-1 inhibitory activity through in vitro enzymatic experiments. The results showed that the 11 beta HSD1 inhibitory activity of compounds 5g and 5h was stable and efficient. Molecular docking studies revealed compounds 5g (-9.758) and 5h (-8.495) to have a stable binding patterns to the human 11-Beta-Hydroxysteroid dehydrogenase-1.
引用
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页数:9
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