Synthetic Organic and Medicinal Chemistry Laboratory, Department of Chemistry, Punjabi University, Patiala 147002, Punjab, India.
Department of Basic and Applied Sciences, Punjabi University, Patiala 147002, Punjab, India.
Comput Biol Chem. 2018 Feb;72:45-52. doi: 10.1016/j.compbiolchem.2017.12.010. Epub 2017 Dec 30.
A novel series of N-substituted-benzimidazolyl linked para substituted benzylidene based molecules containing three pharmacologically potent hydrogen bonding parts namely; 2,4-thiazolidinedione (TZD: a 2,4-dicarbonyl), diethyl malonate (DEM: a 1,3-diester and an isooxazolidinedione analog) and methyl acetoacetate (MAA: a β-ketoester) (6a-11b) were synthesized and evaluated for in vitro α-glucosidase inhibition. The structure of the novel synthesized compounds was confirmed through the spectral studies (LC-MS, H NMR, C NMR, FT-IR). Comparative evaluation of these compounds revealed that the compound 9b showed maximum inhibitory potential against α-amylase and α-glucosidase giving an IC value of 0.54 ± 0.01 μM. Furthermore, binding affinities in terms of G score values and hydrogen bond interactions between all the synthesized compounds and the AA residues in the active site of the protein (PDB code: 3TOP) to that of Acarbose (standard drug) were explored with the help of molecular docking studies. Compound 9b was considered as promising candidate of this series.
合成了一系列新型 N-取代苯并咪唑基连接的对取代苯亚甲基基分子，其中包含三个药理学上有效的氢键部分，即：2,4-噻唑烷二酮（TZD：2,4-二羰基）、丙二酸二乙酯（DEM：1,3-二酯和异噁唑烷二酮类似物）和乙酰乙酸甲酯（MAA：β-酮酯）（6a-11b），并对其体外α-葡萄糖苷酶抑制活性进行了评价。通过光谱研究（LC-MS、H NMR、C NMR、FT-IR）证实了新型合成化合物的结构。对这些化合物进行比较评估表明，化合物 9b 对α-淀粉酶和α-葡萄糖苷酶表现出最大的抑制潜力，IC 值为 0.54±0.01μM。此外，通过分子对接研究，还探索了所有合成化合物与蛋白质活性部位 AA 残基（PDB 代码：3TOP）之间的结合亲和力（以 G 评分值表示）和氢键相互作用，以及与阿卡波糖（标准药物）的相互作用。化合物 9b 被认为是该系列中很有前途的候选药物。
