Nehra Bhupender, Kumar Manoj, Singh Sumitra, Chawla Viney, A Chawla Pooja, Grover Parul
Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar-125001, Haryana, India.
University Institute of Pharmaceutical Sciences and Research, BFUHS University, Faridkot -151203, Punjab, India.
Curr Med Chem. 2024 May 23. doi: 10.2174/0109298673301266240506083014.
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.
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.
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.
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.
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.
感染仍然是一个重大的全球健康问题,数百万新的传染病病例和死亡事件不断发生。目前,化学预防和化疗是主要的治疗方法,但副作用和毒性带来了挑战。致病微生物已经对抗菌药物产生了耐药性。含氮杂环骨架在药物发现中具有潜力,并在制药、化妆品和农用化学品等各个领域得到探索。为了尽量减少抗菌药物耐药性,需要设计出具有更高选择性和最小细胞毒性的强效、更安全的抗菌先导化合物。
本综述旨在概述含氮杂环衍生物药物化学方面的一些最新进展,目的如下:(1) 揭示2015年至2023年最近八年的文献报道,描述含氮杂环衍生物的抗菌潜力,包括吡唑、吡唑啉、咪唑、四唑和喹啉;(2) 简述含氮杂环衍生物药物化学针对其抗菌特性的最新进展;(3) 总结含氮杂环分子的结构特征与药理作用的完全相关性,包括计算机模拟以及机理研究,为先导分子的产生提供思路。
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,展示了含氮杂环分子的抗菌潜力。相比之下,不同文章中的计算机模拟计算分析也有助于预测强效分子的构效关系。
含氮杂环涉及一系列具有敏锐抗菌效力的天然到合成类似物。迫切需要生成新的含氮杂环分子,以便以更具针对性的选择性和特异性来应对微生物的耐药性。
为了限制与它们相关的副作用,并对抗微生物对当前药物治疗方案产生的耐药性,开发新型含氮杂环类抗菌剂至关重要。本综述将先导化合物中存在的结构单元与其有前景的抗菌作用联系起来。