Scholarlink

<p>Myeloperoxidase (MPO), a key pro-inflammatory enzyme, plays a pivotal role in the progression of cardiovascular diseases (CVD), notably atherosclerosis. Herein, we report the synthesis and biological screening of nitro- and amino-substituted benzo[1,3]dioxole-5-carboxamide derivatives (<b>3a</b>–<b>3</b><b>h</b> and <b>4a</b>–<b>4</b><b>h</b>) as potential MPO inhibitors. Most molecules displayed favorable pharmacokinetic properties and exhibited promising in vitro inhibitory activity with compounds <b>3f</b> (IC<sub>50</sub> = 10 ± 0.27 μM) and <b>4f</b> (IC<sub>50</sub> = 11.53 ± 0.12 μM) emerging as potent leads for MPO inhibition. <b>3f</b> and <b>4f</b> significantly attenuated HOCl production in the taurine assay, effectively prevented oxidation of HDL, and controlled lipid peroxidation, highlighting their anti-atherogenic potential. The lead molecules effectively modulate ROS levels and demonstrate lower cytotoxicity in the MTT assay. Collectively, these findings showcase benzodioxole-carboxamide scaffolds as a new chemotype of MPO inhibitors, offering a promising avenue for the development of MPO-targeted anti-inflammatory therapeutics.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Reversible Myeloperoxidase Inhibition by Benzodioxole Carboxamides: Insights from In Silico and InVitro Studies

  • 期刊论文

  • 发表日期：

    2025年9月12日

查看全文
  • Reshma Rajan,
  • Sambantham Karthikeyan,
  • Rajagopal Desikan

摘要

Myeloperoxidase (MPO), a key pro-inflammatory enzyme, plays a pivotal role in the progression of cardiovascular diseases (CVD), notably atherosclerosis. Herein, we report the synthesis and biological screening of nitro- and amino-substituted benzo[1,3]dioxole-5-carboxamide derivatives (3a–3h and 4a–4h) as potential MPO inhibitors. Most molecules displayed favorable pharmacokinetic properties and exhibited promising in vitro inhibitory activity with compounds 3f (IC50 = 10 ± 0.27 μM) and 4f (IC50 = 11.53 ± 0.12 μM) emerging as potent leads for MPO inhibition. 3f and 4f significantly attenuated HOCl production in the taurine assay, effectively prevented oxidation of HDL, and controlled lipid peroxidation, highlighting their anti-atherogenic potential. The lead molecules effectively modulate ROS levels and demonstrate lower cytotoxicity in the MTT assay. Collectively, these findings showcase benzodioxole-carboxamide scaffolds as a new chemotype of MPO inhibitors, offering a promising avenue for the development of MPO-targeted anti-inflammatory therapeutics.