Tse-Dinh Yuk-Ching
Department of Chemistry & Biochemistry, Florida International University, 11200 SW 8 St, Miami, FL 33199, USA.
Future Med Chem. 2015;7(4):459-71. doi: 10.4155/fmc.14.157.
Resistance of bacterial pathogens to current antibiotics has grown to be an urgent crisis. Approaches to overcome this challenge include identification of novel targets for discovery of new antibiotics. Bacterial topoisomerase I is present in all bacterial pathogens as a potential target for bactericidal topoisomerase poison inhibitors. Recent efforts have identified inhibitors of bacterial topoisomerase I with antibacterial activity. Additional research on the mode of action and binding site of these inhibitors would provide further validation of the target and establish that bacterial topoisomerase I is druggable. Bacterial topoisomerase I is a potentially high value target for discovery of new antibiotics. Demonstration of topoisomerase I as the cellular target of an antibacterial compound would provide proof-of-concept validation.
细菌病原体对现有抗生素的耐药性已发展成为一个紧迫的危机。克服这一挑战的方法包括确定发现新抗生素的新靶点。细菌拓扑异构酶I存在于所有细菌病原体中，是杀菌性拓扑异构酶中毒抑制剂的潜在靶点。最近的研究已经确定了具有抗菌活性的细菌拓扑异构酶I抑制剂。对这些抑制剂的作用方式和结合位点进行更多研究将进一步验证该靶点，并确定细菌拓扑异构酶I是可成药的。细菌拓扑异构酶I是发现新抗生素的一个潜在高价值靶点。证明拓扑异构酶I是抗菌化合物的细胞靶点将提供概念验证。
