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卡洛芬新型N-酰腙衍生物作为潜在抗结核药物的合成与表征

Synthesis and Characterization of New N-acyl Hydrazone Derivatives of Carprofen as Potential Tuberculostatic Agents.

作者信息

Vlad Ilinca Margareta, Nuță Diana Camelia, Căproiu Miron Theodor, Dumitrașcu Florea, Kapronczai Eleonóra, Mük Georgiana Ramona, Avram Speranta, Niculescu Adelina Gabriela, Zarafu Irina, Ciorobescu Vanesa Alexandra, Brezeanu Ana Maria, Limban Carmen

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia no. 6, 020956 Bucharest, Romania.

"C. D. Nenitzescu" Institute of Organic and Supramolecular Chemistry, 202B Splaiul Independenței, 060023 Bucharest, Romania.

出版信息

Antibiotics (Basel). 2024 Feb 23;13(3):212. doi: 10.3390/antibiotics13030212.

Abstract

N-acyl hydrazone (NAH) is recognized as a promising framework in drug design due to its versatility, straightforward synthesis, and attractive range of biological activities, including antimicrobial, antitumoral, analgesic, and anti-inflammatory properties. In the global context of increasing resistance of pathogenic bacteria to antibiotics, NAHs represent potential solutions for developing improved treatment alternatives. Therefore, this research introduces six novel derivatives of ()-N'-benzylidene-2-(6-chloro-9-carbazol-2-yl)propanehydrazide, synthesized using a microwave-assisted method. In more detail, we joined two pharmacophore fragments in a single molecule, represented by an NSAID-type carprofen structure and a hydrazone-type structure, obtaining a new series of NSAID-N-acyl hydrazone derivatives that were further characterized spectrally using FT-IR, NMR, and HRMS investigations. Additionally, the substances were assessed for their tuberculostatic activity by examining their impact on four strains of , including two susceptible to rifampicin (RIF) and isoniazid (INH), one susceptible to RIF and resistant to INH, and one resistant to both RIF and INH. The results of our research highlight the potential of the prepared compounds in fighting against antibiotic-resistant strains.

摘要

N-酰基腙(NAH)因其多功能性、合成简便以及具有包括抗菌、抗肿瘤、镇痛和抗炎特性在内的一系列有吸引力的生物活性,而被认为是药物设计中一个有前景的框架。在病原菌对抗生素耐药性不断增加的全球背景下,NAH代表了开发改进治疗替代方案的潜在解决方案。因此,本研究介绍了六种新型的()-N'-亚苄基-2-(6-氯-9-咔唑-2-基)丙烷酰肼衍生物,采用微波辅助方法合成。更详细地说,我们将两个药效团片段连接在一个分子中,分别由非甾体抗炎药(NSAID)类型的卡洛芬结构和腙类结构代表,得到了一系列新的NSAID-N-酰基腙衍生物,并通过傅里叶变换红外光谱(FT-IR)、核磁共振(NMR)和高分辨率质谱(HRMS)研究对其进行了光谱表征。此外,通过检测这些物质对四种结核分枝杆菌菌株的影响来评估它们的抑菌活性,这四种菌株包括两种对利福平(RIF)和异烟肼(INH)敏感的菌株、一种对RIF敏感但对INH耐药的菌株以及一种对RIF和INH均耐药的菌株。我们的研究结果突出了所制备化合物对抗生素耐药结核分枝杆菌菌株的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9056/10967372/709a1e41fd28/antibiotics-13-00212-g001.jpg

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