Abstract

A new series of rhodanines with phenyl substitution at the fifth position of rhodanine ring were designed targeting the PPAR-γ receptor for their possible antihyperglycemic activity. The rational design and molecular modeling studies were performed against PPAR-γ (PDB ID: 2PRG). The compounds were docked and thereafter subjected for the synthesis via dithiocarbamate formation followed by Knoevenagel condensation. Structures were confirmed by IR, NMR and Mass spectral analysis. All synthesized compounds were screened for in vitro glucose uptake assay using isolated hepatocytes. The Compounds A5 and B5 having N-(p-methoxy benzyl) at third position of rhodanine ring showed good glucose uptake activity. These two compounds were further studied for the in vivo antihyperglycemic study against dexamethasone induced insulin resistance. The compounds were tested at single dose level of 10 mg/kg, per oral. The compound B5 showed significant antihyperglycemic activity when compared with the standard drug, pioglitazone. The illustration, about the molecular design, synthesis, analysis, glucose uptake study and in vivo antihyperglycemic activity is reported here along with the structure activity relationships.

摘要

设计了一系列在罗丹宁环第五位具有苯基取代的新罗丹宁，以 PPAR-γ 受体为目标，因为它们可能具有抗高血糖活性。针对 PPAR-γ (PDB ID: 2PRG) 进行了合理设计和分子建模研究。将化合物对接，然后通过形成二硫代氨基甲酸酯进行合成，然后进行 Knoevenagel 缩合。通过IR、NMR和质谱分析确认结构。使用分离的肝细胞对所有合成的化合物进行体外葡萄糖摄取测定。化合物A5和B5具有N -( p-甲氧基苄基）在罗丹宁环的第三位显示出良好的葡萄糖摄取活性。这两种化合物被进一步研究用于针对地塞米松诱导的胰岛素抵抗的体内抗高血糖研究。以每次口服 10 mg/kg 的单剂量水平测试化合物。与标准药物吡格列酮相比，化合物B5显示出显着的抗高血糖活性。本文报道了关于分子设计、合成、分析、葡萄糖摄取研究和体内抗高血糖活性的插图以及结构活性关系。