Synthesis of Cyclic Hexapeptides via the Hydrazide Method and Evaluation of Their Antibacterial Activities.

IF 4.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules Pub Date : 2025-06-03 DOI:10.3390/molecules30112444

Yunfei Cui, Meng Liu, Binghui Ruan, Zhouyuji Liao, Xue Tang, Dongting Zhangsun, Yong Wu, Sulan Luo

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Abstract

Antimicrobial peptides (AMPs) have emerged as promising candidates in the fight against multidrug-resistant pathogens due to their broad-spectrum antimicrobial activity and low potential for resistance development. However, their clinical application is limited by poor stability and susceptibility to enzymatic degradation. This study aims to address these limitations by synthesizing a series of cyclic hexapeptides using the hydrazide method and evaluating their antimicrobial activity and stability. The hydrazide method facilitated the synthesis of 11 cyclic peptides through a reaction between C-terminal hydrazides and cysteine-containing peptides. Antimicrobial assays showed that Cy-f2 and Cy-f4 exhibited potent inhibitory effects against different kinds of bacteria, including E. coli, Staphylococcus aureus, and S. aureus. Hemolysis assays revealed minimal red blood cell lysis at effective antimicrobial concentrations, indicating good biocompatibility. Stability tests demonstrated improved stability of the cyclic peptides compared to linear counterparts in SGF and 80 °C. In conclusion, the cyclic hexapeptides synthesized in this study demonstrate excellent antimicrobial activity, enhanced stability, and low toxicity, suggesting their potential as new candidates for treating drug-resistant bacterial infections.

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酰肼法合成环六肽及其抗菌活性评价。

抗菌肽因其广谱抗菌活性和较低的耐药潜力而成为抗多药耐药病原体的重要候选药物。然而，它们的临床应用受到稳定性差和易被酶降解的限制。本研究旨在利用肼法合成一系列环六肽，并对其抗菌活性和稳定性进行评价，以解决这些局限性。该方法通过c端肼与含半胱氨酸肽的反应，合成了11个环肽。抑菌实验表明，Cy-f2和Cy-f4对大肠杆菌、金黄色葡萄球菌和金黄色葡萄球菌等多种细菌均有较强的抑制作用。溶血试验显示，在有效的抗菌素浓度下，红细胞溶解最小，表明良好的生物相容性。稳定性测试表明，与线性肽相比，环状肽在SGF和80°C下的稳定性有所提高。综上所述，本研究合成的环六肽具有良好的抗菌活性，增强的稳定性和低毒性，表明它们有潜力成为治疗耐药细菌感染的新候选物。

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

Molecules 化学-有机化学

CiteScore

7.40

自引率

8.70%

发文量

7524

审稿时长

1.4 months

期刊介绍： Molecules (ISSN 1420-3049, CODEN: MOLEFW) is an open access journal of synthetic organic chemistry and natural product chemistry. All articles are peer-reviewed and published continously upon acceptance. Molecules is published by MDPI, Basel, Switzerland. Our aim is to encourage chemists to publish as much as possible their experimental detail, particularly synthetic procedures and characterization information. There is no restriction on the length of the experimental section. In addition, availability of compound samples is published and considered as important information. Authors are encouraged to register or deposit their chemical samples through the non-profit international organization Molecular Diversity Preservation International (MDPI). Molecules has been launched in 1996 to preserve and exploit molecular diversity of both, chemical information and chemical substances.