Synthesis, Antimycobacterial Activity, and Computational Insight of Novel 1,4-Benzoxazin-2-one Derivatives as Promising Candidates against Multidrug-Resistant Mycobacterium Tuberculosis.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-05-14 DOI:10.1002/cmdc.202500073

Maria Grazia Mamolo, Emanuele Carosati, Diletta Pasin, Alessandro De Logu, Gianluigi Cabiddu, Marko Jukič, Daniele Zampieri

引用次数: 0

Abstract

In the search for new antitubercular agents, a series of 1,4-benzoxazinone-based compounds is designed, synthesized, and evaluated. These molecules show potent antimycobacterial activity, with a minimum inhibitory concentration between 2 and 8 μg mL^-1. This interesting profile includes activity against several drug-resistant strains and minimal cytotoxicity against mammalian Vero cells. Structural similarities with analogs from the literature are reinforced by molecular docking and molecular dynamics simulations, suggesting that inhibition of the menaquinone-B enzyme as a potential mechanism of action. In addition, the active compounds exhibit favorable predicted Absorption, Distribuition, Metabolism, and Excretion (ADME) properties, indicating their potential for oral administration in humans.

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新型1,4-苯并恶嗪-2- 1衍生物的合成、抑菌活性及计算分析

为了寻找新的抗结核药物，我们设计、合成并评价了一系列基于1,4-苯并恶嗪酮的化合物。这些分子具有较强的抑菌活性，MIC在2 ~ 8 μg/mL之间。这个有趣的特征包括对几种耐药菌株的活性和对哺乳动物Vero细胞的最小细胞毒性。通过分子对接和分子动力学模拟，增强了与文献中类似物的结构相似性，表明抑制MenB酶是一种潜在的作用机制。此外，活性化合物表现出良好的预测ADME特性，表明它们具有口服给药的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

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