Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Bioorg Chem. 2018 Feb;76:98-112. doi: 10.1016/j.bioorg.2017.11.010. Epub 2017 Nov 16.
We herein report the design, synthesis and molecular docking studies of 2,4-thiazolidinedione derivatives containing benzene sulphonyl group which are docked against the Peroxisome Proliferator Activated Receptor (PPARγ) target. Compound 7p was most effective in lowering the blood glucose level as compared to standard drugs pioglitazone and rosiglitazone. Compound 7p exhibited potent PPAR-γ transactivation of 61.2% with 1.9 folds increase in gene expression. In molecular docking studies 7p showed excellent interactions with amino acids TYR 473, SER 289, HIE 449, TYR 327, ARG 288, MET 329 and LEU 228. Compound 7p did not cause any damage to the liver without any noteworthy weight gain and may be considered as promising candidates for the development of new antidiabetic agents.
我们在此报告了含有苯磺酰基的 2,4-噻唑烷二酮衍生物的设计、合成和分子对接研究,这些衍生物对接了过氧化物酶体增殖物激活受体(PPARγ)靶点。与标准药物吡格列酮和罗格列酮相比,化合物 7p 最有效地降低了血糖水平。化合物 7p 对 PPAR-γ 的转录激活作用最强,基因表达增加了 1.9 倍。在分子对接研究中,7p 与氨基酸 TYR 473、SER 289、HIE 449、TYR 327、ARG 288、MET 329 和 LEU 228 表现出极好的相互作用。化合物 7p 不会对肝脏造成任何损害,也不会引起明显的体重增加,因此可能被认为是开发新型抗糖尿病药物的有前途的候选药物。