Kumar Gautam, Kiran Tudu Asha
Department of Natural Products, Chemical Sciences, National Institute of Pharmaceutical Education and Research-Hyderabad, Hyderabad, Balanagar, Telangana 500037, India.
Department of Natural Products, Chemical Sciences, National Institute of Pharmaceutical Education and Research-Hyderabad, Hyderabad, Balanagar, Telangana 500037, India.
Bioorg Med Chem. 2023 Feb 15;80:117187. doi: 10.1016/j.bmc.2023.117187. Epub 2023 Jan 27.
Staphylococcus aureus (S. aureus) is a pathogen responsible for various community and hospital-acquired infections with life-threatening complications like bacteraemia, endocarditis, meningitis, liver abscess, and spinal cord epidural abscess. Antibiotics have been used to treat microbial infections since the introduction of penicillin in 1940. In recent decades, the abuse and misuse of antibiotics in humans, animals, plants, and fungi, including the treatment of non-microbial diseases, have led to the rapid emergence of multidrug-resistant pathogens with increased virulence. Bacteria have developed several complementary mechanisms to avoid the effects of antibiotics. These mechanisms include chemical transformations and enzymatic inactivation of antibiotics, modification of antibiotics' target site, and reduction of intracellular antibiotics concentration by changes in membrane permeability or by the overexpression of efflux pumps (EPs). The strategy to check antibiotic resistance includes synthesis of the antibiotic analogues, or antibiotics are given in combination with the adjuvant. The inhibitors of multidrug EPs are considered promising alternative therapeutic options with the potential to revive the effects of antibiotics and reduce bacterial virulence. Natural products played a vital role in drug discovery and significantly contributed to the area of infectious diseases. Also, natural products provide lead compounds that sometimes need modification based on structural and biological properties to meet the drug criteria. This review discusses natural products and their derived compounds as NorA efflux pump inhibitors (EPIs).
金黄色葡萄球菌是一种可引发各种社区获得性和医院获得性感染的病原体，会导致菌血症、心内膜炎、脑膜炎、肝脓肿和脊髓硬膜外脓肿等危及生命的并发症。自1940年青霉素问世以来，抗生素一直被用于治疗微生物感染。近几十年来，抗生素在人类、动物、植物和真菌中的滥用和误用，包括用于治疗非微生物疾病，导致了具有更高毒力的多重耐药病原体迅速出现。细菌已经发展出几种互补机制来避免抗生素的影响。这些机制包括抗生素的化学转化和酶失活、抗生素靶位点的修饰，以及通过改变膜通透性或过表达外排泵来降低细胞内抗生素浓度。对抗生素耐药性的应对策略包括合成抗生素类似物，或将抗生素与佐剂联合使用。多重耐药外排泵抑制剂被认为是有前景的替代治疗选择，有可能恢复抗生素的疗效并降低细菌毒力。天然产物在药物发现中发挥了至关重要的作用，并对传染病领域做出了重大贡献。此外，天然产物提供了先导化合物，有时需要根据结构和生物学性质进行修饰以符合药物标准。本综述讨论了作为诺氟沙星外排泵抑制剂（EPI）的天然产物及其衍生化合物。
