Methoxyphenol derivatives as reversible inhibitors of myeloperoxidase as potential antiatherosclerotic agents.
Methoxyphenol derivatives as reversible inhibitors of myeloperoxidase as potential antiatherosclerotic agents.
复制标题
DOI：
10.4155/fmc-2019-0080
复制
发表时间：
2019-11
影响因子：
4.2
通讯作者：
Premkumar Jayaraj;C. Narasimhulu;A. Maiseyeu;Rekha Durairaj;Shashidhar N. Rao;S. Rajagopalan;S. Parthasarathy;Rajagopal Desikan
中科院分区：
文献类型：
--
作者：
Premkumar Jayaraj;C. Narasimhulu;A. Maiseyeu;Rekha Durairaj;Shashidhar N. Rao;S. Rajagopalan;S. Parthasarathy;Rajagopal Desikan
目的：评价新的化学实体，阿魏酸支架的基础上，可逆髓过氧化物酶抑制剂（MPOI）。方法和结果：以MPO蛋白作为几种阿魏酸类似物的靶标进行计算机对接研究，然后进行多次体外测定以验证该方法。两个先导化合物2a和3的最佳对接和IC_（50）值分别为-7.95 kcal/mol，0.9 μM和-8.35 kcal/mol，8.5 μM。这些MPOIs能够抑制高密度脂蛋白的氧化，并进一步促进高密度脂蛋白的功能。结论：铅类似物是有效的MPO，对MPO介导的氧化以及炎症途径发挥特异性作用。它还作为胆固醇流出的促进剂，揭示了动脉粥样硬化治疗的药理学方法。
Aim: To evaluate new chemical entities, based on ferulic acid scaffolds, as reversible myeloperoxidase inhibitors (MPOI). Methodology & results: In silico docking studies are performed with MPO protein as a target for several ferulic acid analogs followed by multiple in vitro assays to validate this approach. Two lead compounds 2a and 3 are identified with optimum docking and IC50 values: -7.95 kcal/mol, 0.9 μM and -8.35 kcal/mol, 8.5 μM, respectively. These MPOIs are able to inhibit oxidation of high-density lipoprotein and further promoted functionality of high-density lipoprotein. Conclusion: Lead analogs are potent MPOIs that exert specific effects on MPO-mediated oxidation as well as inflammatory pathways. It also acts as promoters of cholesterol efflux that sheds light on pharmacological approach in atherosclerosis treatment.