腙衍生物对念珠菌属的抗真菌和抗生物膜作用

IF 5.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Pierre Popczyk, Alina Ghinet, Clovis Bortolus, Laure Kamus, Marc F Lensink, Jérôme de Ruyck, Boualem Sendid, Faustine Dubar
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引用次数: 0

摘要

在世界范围内,侵袭性念珠菌病是卫生系统的一个负担,原因包括患者管理困难、对现有疗法的抗药性增加以及天然抗性念珠菌物种的出现。在这种情况下,迫切需要开发创新的抗真菌药物。在侵袭性念珠菌病期间,酵母菌在人类宿主体内会受到许多压力(氧化、热、渗透)。为了抵御这些压力,酵母开发了不同的策略,特别是三卤糖的生物合成。TPS2 是一种参与曲哈糖生物合成的酶,从 TPS2 的三维结构数据出发,我们发现腙是设计新型抗真菌药物的一个有趣支架。有趣的是,我们的腙衍生物对白色念珠菌属具有抗真菌和抗生物膜作用,在体外和体内模型(Galleria mellonella)中无毒。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antifungal and anti-biofilm effects of hydrazone derivatives on Candida spp.

Worldwide, invasive candidiasis are a burden for the health system due to difficulties to manage patients, to the increasing of the resistance of the current therapeutics and the emergence of naturally resistant species of Candida. In this context, the development of innovative antifungal drugs is urgently needed. During invasive candidiasis, yeast is submitted to many stresses (oxidative, thermic, osmotic) in the human host. In order to resist in this context, yeast develops different strategy, especially the biosynthesis of trehalose. Starting from the 3D structural data of TPS2, an enzyme implicated in trehalose biosynthesis, we identified hydrazone as an interesting scaffold to design new antifungal drugs. Interestingly, our hydrazone derivatives which demonstrate antifungal and anti-biofilm effects on Candida spp., are non-toxic in in vitro and in vivo models (Galleria mellonella).

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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