Synthesis of New Glycometronidazole Compounds With Antifungal and Antifungal Biofilm Activity

IF 3.3 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rayssa de Cassia Alves Iemini, Ana Laura Marques Trinca, Monique Dias Benedetti, Cleydson Finotti Cordeiro, Alessandro Vieira Ferreira, Amanda Latércia Tranches Dias, Ivo Santana Caldas, Jamie Anthony Hawkes, Diogo Teixeira Carvalho, Lucas Lopardi Franco
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Abstract

Carbohydrates are well known to be one of the most abundant and structurally diverse natural organic compounds, and they are of great importance as an energy source and as structural components of cell walls in different organisms. They are involved in various biological and pathological processes, including homeostasis, cell–cell interaction, cell migration, cell development, bacterial and viral infection, inflammation, immunology, and cancer metastasis. The variety of these properties is a result of the structural diversity found in carbohydrates. The chemistry of carbohydrates involved in the diagnosis and treatment of diseases has attracted increasing attention from researchers, which is why they should be one of the main focuses in new drug discovery. This study focuses on the synthesis of new glycotriazole–metronidazole compounds as antifungal agents and antifungal biofilm agents, from the glycosylation of metronidazole with various carbohydrates (d-glucose, d-galactose, d-N-acetylglucosamine, and d-lactose). Our hypothesis is that the glycosides could be taken into fungal biofilms through recognition by glycoreceptors and transporters, carrying the active residue with them. In a low-oxygen environment, the nitro group would then undergo bioreduction leading to the formation of toxic radicals potentially resulting in the destruction or paralysis of biofilm formation—essentially functioning as a bioactive “Trojan horse.” The compounds were obtained via a click chemistry reaction using a triazole connector, and the subsequent antifungal tests showed good results for a number of compounds. In silico studies demonstrated positive data for all synthesized compounds, and, in general, they present low toxicological risks.

Abstract Image

具有抗真菌和抗真菌生物膜活性的新型糖新硝唑化合物的合成
碳水化合物是最丰富、结构最多样的天然有机化合物之一,在不同生物体内作为能量来源和细胞壁结构成分具有重要意义。它们参与各种生物和病理过程,包括体内平衡、细胞-细胞相互作用、细胞迁移、细胞发育、细菌和病毒感染、炎症、免疫和癌症转移。这些特性的多样性是碳水化合物结构多样性的结果。碳水化合物在疾病诊断和治疗中的化学作用越来越受到研究人员的关注,这就是为什么它们应该成为新药开发的主要焦点之一。本研究将甲硝唑与多种碳水化合物(d-葡萄糖、d-半乳糖、d- n -乙酰氨基葡萄糖和d-乳糖)糖基化,合成新的糖三唑-甲硝唑类化合物作为抗真菌剂和抗真菌生物膜剂。我们的假设是,糖苷可以通过糖受体和转运体的识别进入真菌生物膜,并携带活性残基。在低氧环境中,硝基会发生生物还原,导致有毒自由基的形成,可能导致生物膜形成的破坏或瘫痪——本质上是一个生物活性的“特洛伊木马”。这些化合物是通过使用三唑连接物的咔嗒化学反应得到的,随后的抗真菌测试显示了许多化合物的良好效果。计算机研究表明,所有合成化合物的数据都是阳性的,总的来说,它们具有较低的毒理学风险。
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
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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