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新型哌嗪和吗啉衍生物:质谱表征及其抗菌活性评价。

New piperazine and morpholine derivatives: Mass spectrometry characterization and evaluation of their antimicrobial activity.

机构信息

Università degli Studi della Basilicata, Dipartimento di Scienze, Viale dell'Ateneo Lucano 10, Potenza, Italy.

Università degli Studi della Basilicata, Dipartimento di Scienze, Viale dell'Ateneo Lucano 10, Potenza, Italy; Spinoff TNcKILLERS, Viale Dell'Ateneo Lucano 10, Potenza 85100, Italy.

出版信息

J Pharm Biomed Anal. 2024 Aug 15;246:116202. doi: 10.1016/j.jpba.2024.116202. Epub 2024 May 12.

DOI:10.1016/j.jpba.2024.116202
PMID:38820833
Abstract

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain compounds with fewer side effects, at the same time effectively overcoming the problem of antimicrobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important support for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of Fourier transform-ion cyclotron resonance (FT-ICR) and Linear Trap Quadrupole (LTQ) mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribution and MS spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds' antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

摘要

最近,药物研究的重点是设计对多种菌株具有更高选择性的新型抗菌药物。主要问题是能否获得副作用更少的化合物,同时有效地克服抗菌药物耐药性的问题。几种解决方案包括从哌嗪或吗啉核心单元出发合成新的药效团。基于质谱的技术为新合成化合物的结构表征提供了重要支持,有助于设计针对各种医疗状况的更安全、更有效的药物。在这里,我们合成了两个新的哌嗪衍生物和四个新的吗啉衍生物,并通过傅里叶变换-离子回旋共振(FT-ICR)和线性阱四极杆(LTQ)质谱的综合方法对其进行了结构表征。高分辨率和低分辨率质谱数据(即精确质量测量、同位素分布和 MS 谱)的支持对于确认合成的成功至关重要。我们进一步评估了这些化合物对总共 29 种革兰氏阳性菌和革兰氏阴性菌的抑制活性,以确定作用谱和抗菌效果。结果表明,这些化合物对许多测试的细菌具有抗菌活性,表明它们的抑制作用与不同的化学结构有关,并表明新合成的衍生物可以被认为是有前途的抗菌剂。

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