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3,5-二取代异恶唑啉/异恶唑烷连接的二级磺酰胺衍生物对铜绿假单胞菌的绿色合成及抗生物膜活性。

Green synthesis and anti-biofilm activities of 3,5-disubstituted isoxazoline/isoxazole-linked secondary sulfonamide derivatives on Pseudomonas aeruginosa.

机构信息

Equipe de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculty of Science, B.P. 1014, Geophysics, Natural Patrimony and Green Chemistry (GEOPAC) Research Center, Mohammed V University in Rabat, Morocco.

Univ Rouen Normandie, Université Caen Normandie, Normandie Univ, CBSA UR4312, Laboratoire de microbiologie Communication Bactérienne et Stratégies Anti-Infectieuses, F-76000 Rouen, France.

出版信息

Bioorg Med Chem Lett. 2023 Nov 15;96:129517. doi: 10.1016/j.bmcl.2023.129517. Epub 2023 Oct 12.

DOI:10.1016/j.bmcl.2023.129517
PMID:37838341
Abstract

The search for new classes of antibiotics is a real concern of public health due to the emergence of multi-resistant bacteria strains. We report herein the synthesis and characterization of a new series of 13 molecules combining isoxazoline/isoxazole sulfonamides and hydrazides motives. These molecules were obtained according to a costless eco-friendly procedure, and a one-pot three-step cascade synthesis under ultrasonic cavitation. All the synthesized compounds were fully characterized by HRMS, H NMR, C NMR spectroscopy and HPLC analysis. These new molecules have been evaluated against the major human opportunistic pathogen Pseudomonas aeruginosa to determine their potential to affect its growth and biofilm formation or dispersion. Two derivatives (5a and 6a) demonstrated their ability to destabilize a mature biofilm by about 50 % within 24 h. This may pave the way to the development of a new class of compounds affecting biofilm, which are easy to synthesize according to green chemistry processes.

摘要

由于多耐药菌株的出现,寻找新类别的抗生素是公共卫生的真正关注点。我们在此报告了一系列新的 13 种分子的合成和表征,这些分子结合了异恶唑啉/异恶唑磺酰胺和酰肼基。这些分子是根据一种无成本的环保程序,在超声空化下进行一锅三步级联合成获得的。所有合成的化合物都通过高分辨率质谱、H NMR、C NMR 光谱和 HPLC 分析进行了充分表征。这些新分子已针对主要的人类机会性病原体铜绿假单胞菌进行了评估,以确定它们对其生长和生物膜形成或分散的潜在影响。两种衍生物(5a 和 6a)在 24 小时内表现出大约 50%的能力来破坏成熟的生物膜。这可能为开发影响生物膜的新型化合物铺平道路,这些化合物根据绿色化学工艺很容易合成。

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