Kuranov Sergey, Luzina Olga, Khvostov Mikhail, Baev Dmitriy, Kuznetsova Darya, Zhukova Nataliya, Vassiliev Pavel, Kochetkov Andrey, Tolstikova Tatyana, Salakhutdinov Nariman
N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Reasearch Center of Innovative Medicines, Laboratory for Information Technology in Pharmacology and Computer Modeling of Drugs, Volgograd State Medical University, Ministry of Health of Russian Federation, 400131 Volgograd, Russia.
Pharmaceuticals (Basel). 2020 Nov 19;13(11):404. doi: 10.3390/ph13110404.
A series of bornyl derivatives of -(benzyloxy)phenylpropionic acid were prepared, and their hypoglycemic activities were examined by an oral glucose tolerance test in mice. The results of this test revealed two compounds, and , that can reduce the blood level of glucose similarly to reference compound vildagliptin. Both compounds were tested in an experiment on mice with metabolic disorders: the C57BL/6 strain. Along with hypoglycemic properties, the two compounds showed different abilities to correct lipid metabolism disorders. In silico prediction revealed that the studied substances are most likely bifunctional multitarget hypoglycemic compounds whose mechanism of action is based on a pronounced reduction in insulin resistance and a strong incretin-mimetic effect. The difference in the size of effects of these compounds on biochemical parameters of blood in the experiment on C57BL/6 mice was in good agreement with the computational prediction of the priority ranking of biological targets for these compounds. These results indicate that bornyl derivatives of -(benzyloxy)phenylpropionic acid have a good potential as new agents for diabetes mellitus treatment due to their hypoglycemic and lipid-normalizing properties.
制备了一系列-(苄氧基)苯丙酸的冰片基衍生物,并通过小鼠口服葡萄糖耐量试验检测了它们的降血糖活性。该试验结果显示,有两种化合物(化合物 和化合物 )的降血糖效果与参比化合物维格列汀相似,均可降低血糖水平。这两种化合物在患有代谢紊乱的C57BL/6小鼠品系上进行了实验。除了具有降血糖特性外,这两种化合物在纠正脂质代谢紊乱方面表现出不同的能力。计算机模拟预测表明,所研究的物质很可能是双功能多靶点降血糖化合物,其作用机制基于显著降低胰岛素抵抗和强烈的肠促胰岛素模拟效应。在C57BL/6小鼠实验中,这些化合物对血液生化参数影响大小的差异与这些化合物生物靶点优先级排序的计算预测结果高度吻合。这些结果表明,-(苄氧基)苯丙酸的冰片基衍生物因其降血糖和脂质调节特性,作为治疗糖尿病的新型药物具有良好的潜力。