背景:感染仍然是一个重要的全球健康问题,由于传染病导致数百万新病例和死亡。目前,化学预防和化疗是主要的治疗方法,但是副作用和毒性带来了挑战。病原微生物已经对抗菌药物产生了抗性。含氮杂环支架具有药物发现的潜力,并在药物等各个领域进行了探索,化妆品,和农用化学品。为了尽量减少抗菌药物的耐药性,有必要设计有效的,更安全的抗菌铅化合物具有更高的选择性和最小的细胞毒性。
目的:本综述旨在概述含氮杂环衍生物在药物化学方面的一些最新进展,目的如下:(1)介绍最近八年的文献报道,从2015年到2023年,描述了含氮杂环衍生物的抗微生物潜力,包括吡唑,吡唑啉,咪唑,四唑和喹啉;(2)简要介绍了含氮杂环衍生物的药物化学的最新进展,这些药物化学针对其抗微生物概况;(3)总结了含氮杂环分子的结构特征与药理作用的完整相关性,包括计算机和机理研究,以提供伴随前导分子产生的思路。
方法:含氮杂环分子的抗菌潜力已通过将各种先导候选物的结构特征与其体外和体内抗菌结果相关联来显示。相比之下,来自不同文章的计算机模拟计算分析也有助于预测强效分子的SAR。
结果:含氮杂环涉及一系列天然至合成类似物,具有敏锐的抗微生物效力。为了以更有针对性的选择性和特异性解决微生物中的药物抗性,产生新的含氮杂环分子是一种新兴的需求。
结论:为了限制与之相关的副作用并对抗微生物对当前药物方案的耐药性,新型含氮杂环基抗菌剂是必须开发的。这篇综述将先导化合物中存在的结构单元与其有希望的抗菌作用联系起来。
BACKGROUND: Infection remains a significant global health concern, with millions of new cases and deaths occurring due to infectious diseases. Currently, chemoprophylaxis and chemotherapy are the primary treatments, but side effects and toxicities pose challenges. Pathogenic microorganisms have developed resistance to
antimicrobial medications. Nitrogen containing heterocyclic scaffolds possess the potential in drug discovery and are explored in various fields like pharmaceuticals, cosmetics, and agrochemicals. To minimize
antimicrobial drug resistance, there is a need to design potent, safer
antimicrobial lead compounds with higher selectivity and minimal cytotoxicity.
OBJECTIVE: The present
review aims to outline several recent developments in medicinal chemistry aspect of nitrogenous heterocyclic derivatives with the following purposes: (1) To cast light on the recent literature reports of the last eight years ranging from 2015 to 2023 describing anti-microbial potential of nitrogen-containing heterocyclic derivatives which includes pyrazole, pyrazoline, imidazole, tetrazole and quinoline; (2) To brief the recent developments in the medicinal chemistry of nitrogenous heterocyclic derivatives that is directed towards their anti-microbial profile; (3) To summarize the complete correlation of structural features of nitrogenous heterocyclic molecules with the pharmacological action including in silico as well as mechanistic studies to provide thoughts accompanying the generation of lead molecules.
METHODS: Antimicrobial potential of nitrogenous heterocyclic molecules has been displayed by relating the structural features of various lead candidates with their in vitro as well as in vivo antimicrobial outcomes. In contrast, in silico computational analysis from different articles also helped to predict the SAR of potent molecules.
RESULTS: Nitrogen containing heterocycles are involved in a range of natural to synthetic analogues with keen antimicrobial potency. It is an emerging need to generate new nitrogenous heterocyclic molecules in order to tackle the drug resistance in micro-organisms with more targeted selectivity as well as specificity.
CONCLUSIONS: To limit the side effects associated with them and to combat the microbes acquired resistance towards the current drug regimen, novel nitrogenous heterocycle based antimicrobial agents are essential to be developed. This
review connects the structural units present in lead compounds with their promising
antimicrobial action.