Synthesis, Antimycobacterial Activity and Computational Insight of novel 1,4-Benzoxazin-2-one Derivatives as Promising Candidates Against Multidrug-Resistant M. tuberculosis.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

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

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

引用次数: 0

Abstract

To search for new antitubercular agents, we have designed, synthesized, and evaluated a series of 1,4-benzoxazinone-based compounds. These molecules showed potent antimycobacterial activity, with MIC between 2 and 8 μg/mL. This interesting profile included activity against several drug-resistant strains and minimal cytotoxicity against mammalian Vero cells. Structural similarities with analogs from the literature were reinforced by molecular docking and molecular dynamics simulations, suggesting that inhibition of the MenB enzyme is a potential mechanism of action. In addition, the active compounds exhibited favorable predicted ADME properties, indicating their potential for oral administration to humans.

查看原文本刊更多论文

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。

求助全文

约1分钟内获得全文求助全文

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

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.