Mehta Kunal, Khambete Mihir, Abhyankar Arundhati, Omri Abdelwahab
SVKM's Dr Bhanuben Nanavati College of Pharmacy, Mumbai 400056, India.
Department of Chemistry and Biochemistry, The Novel Drug and Vaccine Delivery Systems Facility, Laurentian University, Sudbury, ON P3E 2C6, Canada.
Pharmaceuticals (Basel). 2023 Mar 1;16(3):377. doi: 10.3390/ph16030377.
Mur enzymes serve as critical molecular devices for the synthesis of UDP-MurNAc-pentapeptide, the main building block of bacterial peptidoglycan polymer. These enzymes have been extensively studied for bacterial pathogens such as and . Various selective and mixed Mur inhibitors have been designed and synthesized in the past few years. However, this class of enzymes remains relatively unexplored for (Mtb), and thus offers a promising approach for drug design to overcome the challenges of battling this global pandemic. This review aims to explore the potential of Mur enzymes of Mtb by systematically scrutinizing the structural aspects of various reported bacterial inhibitors and implications concerning their activity. Diverse chemical scaffolds such as thiazolidinones, pyrazole, thiazole, etc., as well as natural compounds and repurposed compounds, have been reviewed to understand their in silico interactions with the receptor or their enzyme inhibition potential. The structural diversity and wide array of substituents indicate the scope of the research into developing varied analogs and providing valuable information for the purpose of modifying reported inhibitors of other multidrug-resistant microorganisms. Therefore, this provides an opportunity to expand the arsenal against Mtb and overcome multidrug-resistant tuberculosis.
Mur酶是合成UDP-胞壁酰五肽的关键分子装置,UDP-胞壁酰五肽是细菌肽聚糖聚合物的主要组成部分。这类酶已针对诸如[具体细菌名称1]和[具体细菌名称2]等细菌病原体进行了广泛研究。在过去几年中,已设计并合成了各种选择性和混合性的Mur抑制剂。然而,对于结核分枝杆菌(Mtb)而言,这类酶仍相对未被充分探索,因此为药物设计提供了一种有前景的方法,以应对抗击这一全球大流行病所面临的挑战。本综述旨在通过系统审视各种已报道的细菌抑制剂的结构方面及其活性相关影响,来探索结核分枝杆菌Mur酶的潜力。已对多种化学支架,如噻唑烷酮、吡唑、噻唑等,以及天然化合物和重新利用的化合物进行了综述,以了解它们与受体的计算机模拟相互作用或其酶抑制潜力。结构多样性和广泛的取代基表明了开发各种类似物研究的范围,并为修饰其他多重耐药微生物的已报道抑制剂提供了有价值的信息。因此,这提供了一个机会来扩充对抗结核分枝杆菌的武器库并克服多重耐药结核病。