Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, 136119, India.
Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, 151001, India.
Eur J Med Chem. 2019 Nov 15;182:111644. doi: 10.1016/j.ejmech.2019.111644. Epub 2019 Aug 27.
The emergence of drug resistance in infectious microbial strains can be overcome by development of novel drug molecules against unexploited microbial target. The success of Bedaquiline in recent years, as FF ATP synthase inhibitor against XDR and MDR mycobacterium strains, has resulted in further exploration to identify more potent and safe drug molecules against resistant strains. FF ATP synthase is the main energy production enzyme in almost all eukaryotes and prokaryotes. Development of bacterial ATP synthase inhibitors is a safe approach, without causing harm to mammalian cells due to structural difference between bacterial and mammalian ATP synthase target sites. This review emphasizes on providing the structural insights for FF ATP synthase of different prokaryotes and will help in the design of new potent antimicrobial agents with better efficacy. Further, applications of synthetic and natural active antimicrobial ATP synthase inhibitors, reported by different research groups are summarized. Their SAR and mode of actions are also analysed.
耐药性在传染性微生物菌株中的出现可以通过开发针对未开发的微生物靶点的新型药物分子来克服。近年来贝达喹啉的成功，作为一种针对 XDR 和 MDR 分枝杆菌菌株的 FF ATP 合酶抑制剂，进一步促使人们探索识别针对耐药菌株更有效和更安全的药物分子。FF ATP 合酶是几乎所有真核生物和原核生物的主要能量产生酶。开发细菌 ATP 合酶抑制剂是一种安全的方法，由于细菌和哺乳动物 ATP 合酶靶位之间的结构差异，不会对哺乳动物细胞造成伤害。这篇综述强调提供不同原核生物 FF ATP 合酶的结构见解，并有助于设计具有更好疗效的新型强效抗菌药物。此外，还总结了不同研究小组报道的合成和天然活性抗菌 ATP 合酶抑制剂的应用。还分析了它们的 SAR 和作用模式。
