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发现“-(1-(香豆素-3-基)亚乙基)苯磺酰肼”作为一种新型伤口愈合增强剂:合成、生物学评估及分子模拟

Discovery of '-(1-(coumarin-3-yl)ethylidene)benzenesulfonohydrazide as a novel wound healing enhancer: synthesis, biological assessment, and molecular modeling.

作者信息

Khaleel Eman F, Abdelmegeed Heba, Abdel-Razik Abdel-Razik H, Ebaid Manal S, Son Ninh The, Ha Nguyen Xuan, Atef Abdelsattar Ibrahim Hoda, Abdelrahman Mohamed A, Elshamy Abdelsamed I, Dziadek Jarosław, Sabt Ahmed, Eldehna Wagdy M

机构信息

Department of Medical Physiology, College of Medicine, King Khalid University, Asir, Saudi Arabia.

Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Egypt.

出版信息

Front Chem. 2025 Aug 8;13:1621717. doi: 10.3389/fchem.2025.1621717. eCollection 2025.

Abstract

Wound healing poses a considerable challenge in the domain of medical science. In modern clinical practice, there is a growing trend towards using herbal compounds to aid in the repair process. Among these, coumarin, a phytochemical recognized for its antibacterial and wound-healing properties, has attracted significant interest. Consequently, the current research explores the potential benefits of employing coumarin to enhance wound healing in a murine model. The compound '-(1-(7-hydroxy-2-oxo-2-chromen-3-yl)ethylidene)-4-methylbenzene sulfonohydrazide (CBSH) was synthesized through the condensation of 7-hydroxy-3-acetyl coumarin with -toluenesulfonylhydrazide and subsequently assessed for its antibacterial efficacy. CBSH showcased impressive antimicrobial prowess, demonstrating the values of minimum inhibitory concentration (MIC) 50, 40, and 40 μg/mL against the notorious MRSA, the resilient , and the formidable . Subsequent and experiments were performed to assess its impact on the healing of skin wounds. The results indicated that CBSH significantly promotes the migration of skin fibroblast cells and enhances the wound healing process. Additionally, it facilitated the complete re-epithelialization of wounds. The formation of well-structured granulation tissue, along with a decrease in indicators of wound infection, is supported by histological analysis that demonstrates a minimal presence of inflammatory cells compared to untreated wounds. Furthermore, molecular docking studies targeting key proteins involved in skin wound healing (COX-2, 5-LOX, COX-1, and TNF-α) demonstrated that COX-2 exhibited the highest binding affinity for CBSH, along with a stable complex during molecular dynamics simulations. Collectively, the results of this study indicate that CBSH may have a protective effect against infections in skin wounds, attributable to its antimicrobial properties.

摘要

伤口愈合在医学领域是一项颇具挑战性的任务。在现代临床实践中,使用草药化合物辅助修复过程的趋势日益明显。其中,香豆素作为一种具有抗菌和伤口愈合特性的植物化学物质,已引起了广泛关注。因此,当前的研究探索了在小鼠模型中使用香豆素促进伤口愈合的潜在益处。化合物“-(1-(7-羟基-2-氧代-2-色烯-3-基)亚乙基)-4-甲基苯磺酰肼(CBSH)通过7-羟基-3-乙酰香豆素与对甲苯磺酰肼缩合而成,随后评估其抗菌效果。CBSH展现出令人印象深刻的抗菌能力,对臭名昭著的耐甲氧西林金黄色葡萄球菌、顽强的[此处原文缺失细菌名称]和强大的[此处原文缺失细菌名称]的最低抑菌浓度(MIC)值分别为50、40和40μg/mL。随后进行了体内和体外实验,以评估其对皮肤伤口愈合的影响。结果表明,CBSH显著促进皮肤成纤维细胞的迁移,并加速伤口愈合过程。此外,它还促进了伤口的完全重新上皮化。组织学分析支持结构良好的肉芽组织形成,同时伤口感染指标下降,与未处理的伤口相比,炎症细胞的存在极少。此外,针对参与皮肤伤口愈合的关键蛋白(COX-2、5-LOX、COX-1和TNF-α)的分子对接研究表明,COX-2对CBSH表现出最高的结合亲和力,并且在分子动力学模拟过程中形成稳定的复合物。总体而言,本研究结果表明,CBSH可能因其抗菌特性对皮肤伤口感染具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23d4/12370739/d2e74c559e5f/fchem-13-1621717-g001.jpg

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