Kumar Gautam, Engle Kritika
Department of Natural Products, Chemical Sciences, National Institute of Pharmaceutical Education and Research-Hyderabad, Hyderabad, Balanagar, 500037, India.
Nat Prod Rep. 2023 Oct 18;40(10):1608-1646. doi: 10.1039/d2np00084a.
Covering: 2015 to 2022 () is responsible for several community and hospital-acquired infections with life-threatening complications such as bacteraemia, endocarditis, meningitis, liver abscess, and spinal cord epidural abscess. In recent decades, the abuse and misuse of antibiotics in humans, animals, plants, and fungi and the treatment of nonmicrobial diseases have led to the rapid emergence of multidrug-resistant pathogens. The bacterial wall is a complex structure consisting of the cell membrane, peptidoglycan cell wall, and various associated polymers. The enzymes involved in bacterial cell wall synthesis are established antibiotic targets and continue to be a central focus for antibiotic development. Natural products play a vital role in drug discovery and development. Importantly, natural products provide a starting point for active/lead compounds that sometimes need modification based on structural and biological properties to meet the drug criteria. Notably, microorganisms and plant metabolites have contributed as antibiotics for noninfectious diseases. In this study, we have summarized the recent advances in understanding the activity of the drugs or agents of natural origin that directly inhibit the bacterial membrane, membrane components, and membrane biosynthetic enzymes by targeting membrane-embedded proteins. We also discussed the unique aspects of the active mechanisms of established antibiotics or new agents.
2015年至2022年（）导致了多种社区获得性和医院获得性感染，并伴有危及生命的并发症，如菌血症、心内膜炎、脑膜炎、肝脓肿和脊髓硬膜外脓肿。近几十年来，抗生素在人类、动物、植物和真菌中的滥用以及非微生物疾病的治疗导致了多重耐药病原体的迅速出现。细菌细胞壁是一个复杂的结构，由细胞膜、肽聚糖细胞壁和各种相关聚合物组成。参与细菌细胞壁合成的酶是已确定的抗生素靶点，并且仍然是抗生素开发的核心焦点。天然产物在药物发现和开发中起着至关重要的作用。重要的是，天然产物为活性/先导化合物提供了一个起点，这些化合物有时需要根据结构和生物学特性进行修饰以满足药物标准。值得注意的是，微生物和植物代谢产物已作为非传染性疾病的抗生素发挥了作用。在本研究中，我们总结了在理解天然来源的药物或制剂通过靶向膜嵌入蛋白直接抑制细菌膜、膜成分和膜生物合成酶的活性方面的最新进展。我们还讨论了已确立的抗生素或新制剂活性机制的独特方面。
