1,5-Diarylidene-4-Piperidones as Promising Antifungal Candidates Against Cryptococcus neoformans.

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

Antibiotics-Basel Pub Date : 2025-09-01 DOI:10.3390/antibiotics14090883

Elise Courvoisier-Dezord, Hugo Ragusa, Axelle Grandé, Louise Denudt, Yolande Charmasson, Frédéric Dumur, Didier Siri, Marc Maresca, Malek Nechab

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引用次数: 0

Abstract

Background/objectives: The present study investigates the antifungal potential of 1,5-diarylidene-4-piperidones.

Methods: These compounds were synthesized via Claisen-Schmidt condensation, and their antifungal efficacy was tested against Cryptococcus neoformans, a yeast recently qualified as a critical priority pathogen by the World Health Organization, through determination of their minimum inhibitory concentration (MIC). We designed and synthesized a series of piperidones to explore structure-activity relationships.

Results: Systematic modification of the substituent pattern revealed that tetrabutoxy groups exhibited potent activity (MIC of 7.8 µM), surpassing standard antifungals like fluconazole. The selectivity index (SI) values confirmed their safety profile across various human cells. Docking analysis demonstrated that these compounds target sterol 14-demethylase, suggesting potential inhibition of ergosterol synthesis as a mechanism of action. Interestingly, the compounds also demonstrated broad-spectrum activity against other pathogenic yeasts and fungi, including Candida and Aspergillus species, and against fluconazole-resistant strains.

Conclusions: These findings underscore the potential of 1,5-diarylidene-4-piperidones as promising antifungal candidates with a favorable safety profile.

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1,5-二芳基吡啶-4-哌啶酮作为新型隐球菌的抗真菌候选药物。

背景/目的：本研究探讨1,5-二芳基烯-4-哌啶酮的抗真菌潜力。方法：采用Claisen-Schmidt缩合法合成这些化合物，并通过测定其最低抑菌浓度（MIC）对新隐球菌（Cryptococcus neoformans）的抑菌效果进行了测试。隐球菌是一种最近被世界卫生组织认定为重点病原体的酵母。我们设计并合成了一系列的哌啶酮来探索它们的构效关系。结果：对取代基模式的系统修饰表明，四脲基具有强大的活性（MIC为7.8µM），超过氟康唑等标准抗真菌药物。选择性指数（SI）值证实了它们在各种人体细胞中的安全性。对接分析表明，这些化合物靶向甾醇14-去甲基化酶，提示其潜在的抑制麦角甾醇合成的作用机制。有趣的是，这些化合物还显示出对其他致病性酵母和真菌（包括念珠菌和曲霉菌）以及对氟康唑耐药菌株的广谱活性。结论：这些发现强调了1,5-二芳基吡啶-4-哌啶酮作为具有良好安全性的抗真菌候选药物的潜力。

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

Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics

CiteScore

7.30

自引率

14.60%

发文量

1547

审稿时长

11 weeks

期刊介绍： Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.