Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow-226031, Uttar Pradesh, India.
Department of Medicinal and Process Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
Curr Top Med Chem. 2019;19(8):579-593. doi: 10.2174/1568026619666190304130218.
DNA gyrase is a clinically validated drug target, currently targeted only by fluoroquinolone class of antibacterials. However, owing to increasing drug resistance as well as a concomitant reduction in the availability of newer classes of antibiotics, fluoroquinolones are increasingly being over-utilized in order to treat serious infections, including multi-drug resistant tuberculosis. This, in turn, increases the probability of resistance to fluoroquinolones, which is mediated by a single amino acid change in gyrA, leading to class-wide resistance. In this review, we provide an overview of the recent progress in identifying novel scaffolds which target DNA gyrase and provide an update on their discovery and development status.
DNA 回旋酶是一种经过临床验证的药物靶点，目前仅被氟喹诺酮类抗菌药物靶向。然而，由于耐药性的不断增加以及新型抗生素类别的减少，氟喹诺酮类药物的使用越来越多，以治疗严重感染，包括耐多药结核病。这反过来又增加了对氟喹诺酮类药物的耐药性的可能性，这是由 gyrA 中的单个氨基酸变化介导的，导致全类耐药。在这篇综述中，我们提供了一个关于鉴定靶向 DNA 回旋酶的新型支架的最新进展的概述，并更新了它们的发现和开发状况。
