布洛芬与3,5-二芳基吡啶-4-哌啶酮的杂化偶联物:消炎药发现的新途径。

IF 3.4 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-09-03 DOI:10.1002/cmdc.202500342
Julio C Chavez, Adel S Girgis, Marian N Aziz, Shilpi Khurana, Brandon Carr, Guido F Verbeck, Siva S Panda
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引用次数: 0

摘要

非甾体抗炎药(NSAIDs)自1897年问世以来,在治疗炎症、疼痛和发烧方面起着至关重要的作用。尽管非甾体抗炎药被广泛使用,但由于非选择性抑制环氧化酶(COX)同工酶COX-1和COX-2的胃肠道副作用,它们经常面临限制。虽然选择性COX-2抑制剂可以降低胃肠道毒性,但它们会增加心血管风险。本研究研究了新型杂化非甾体抗炎药缀合物的合成和生物学评价,该缀合物含有3,5-二芳二烯-4-哌啶酮、布洛芬和氨基酸。这些杂交分子旨在增强抗炎功效,同时最大限度地减少不良反应。我们评估了合成的化合物对COX的抑制作用及其对炎症介质如白细胞介素-6、肿瘤坏死因子- α和一氧化氮的影响。计算研究包括分子对接和ADME(吸收、分布、代谢和排泄)分析,以阐明作用机制并预测药代动力学性质。研究结果表明,一些杂交偶联物显示出有希望的抗炎特性,需要进一步研究其潜在的治疗应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hybrid Conjugates of Ibuprofen and 3,5-Diarylidene-4-Piperidone: A New Avenue in Anti-Inflammatory Drug Discovery.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been crucial in managing inflammation, pain, and fever since their introduction in 1897. Despite their widespread use, NSAIDs often face limitations due to gastrointestinal side effects from the nonselective inhibition of cyclooxygenase (COX) isoenzymes, COX-1 and COX-2. While selective COX-2 inhibitors reduce gastrointestinal toxicity, they come with increased cardiovascular risks. This study investigates the synthesis and biological evaluation of novel hybrid NSAID conjugates incorporating 3,5-diarylidene-4-piperidinone, ibuprofen, and amino acids. These hybrid molecules are designed to enhance anti-inflammatory efficacy while minimizing adverse effects. The synthesized compounds are evaluated for COX inhibition and their effects on inflammatory mediators such as interleukin-6, tumor necrosis factor-alpha, and nitric oxide. Computational studies, including molecular docking and ADME (absorption, distribution, metabolism, and excretion) analyses, are performed to clarify the mechanisms of action and to predict pharmacokinetic properties. The findings indicate that some hybrid conjugates display promising anti-inflammatory properties, necessitating further investigation for their potential therapeutic applications.

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来源期刊
ChemMedChem
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.
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