Bradbury Barton J, Pucci Michael J
Achillion Pharmaceuticals, Inc., 300 George Street, New Haven, CT 06511, USA.
Curr Opin Pharmacol. 2008 Oct;8(5):574-81. doi: 10.1016/j.coph.2008.04.009. Epub 2008 Jun 12.
Bacterial topoisomerase inhibitors continue to be actively developed as clinical antibacterial agents, largely owing to the success of the currently marketed inhibitors, the quinolones, and the increasing resistance to these agents. New quinolone analogs such as isothiazoloquinolones and quinazolinediones show some potential in overcoming this problem. Quinolones linked to other antibacterial agents such as rifamycins and oxazolidinones are designed to overcome both quinolone-specific resistance and resistance to the coupled agents. Novel inhibitors targeting non-quinolone-binding regions of topoisomerase continue to expand beyond the known coumarin class. The benzimidazoles and pyrazoles have shown promise but have been surpassed into the clinic by novel quinolines. Improved screening techniques and high-throughput methods offer new hope of further expanding the chemical space of topoisomerase inhibitors.
细菌拓扑异构酶抑制剂作为临床抗菌药物仍在积极研发中，这主要归功于目前已上市的抑制剂喹诺酮类药物的成功，以及对这些药物日益增加的耐药性。新的喹诺酮类似物，如异噻唑并喹啉酮和喹唑啉二酮，在克服这一问题方面显示出一定潜力。与其他抗菌药物如利福霉素和恶唑烷酮相连的喹诺酮类药物旨在克服喹诺酮类药物特异性耐药性以及对联合使用药物的耐药性。针对拓扑异构酶非喹诺酮结合区域的新型抑制剂不断扩展，已超出了已知的香豆素类。苯并咪唑类和吡唑类已显示出前景，但已被新型喹啉类药物超越并进入临床应用。改进的筛选技术和高通量方法为进一步扩展拓扑异构酶抑制剂的化学空间带来了新希望。
