新型非喹诺酮类细菌IIA型拓扑异构酶抑制剂抗菌药物研究进展.PDF

. 380 . 中国抗生素杂志2018年4月第43卷第4期 文章编号：1001-8689(2018)04-0380-07 新型非喹诺酮类细菌IIA型拓扑异构酶抑制剂抗菌药物研究进展 曹刚 赵西林 薛云新 王岱* (分子疫苗学和分子诊断学国家重点实验室，厦门大学，厦门361102) 摘要：自1962年第一代喹诺酮类药物萘啶酮酸发明以来，成百上千种可分为四代的喹诺酮衍生物已经被成功合成，并且细 菌IIA型拓扑异构酶(DNA旋转酶和拓扑异构酶IV)已经被确认为该类抗菌药物的作用靶点。先前研究表明：细菌DNA复制过程 对菌体生长与存活至关重要，而这一过程需要DNA旋转酶和拓扑异构酶IV 的共同作用。在过去50多年中，喹诺酮类药物的广泛 使用也说明这一药物作用靶点在临床治疗上的重要性；但是由于对喹诺酮类药物不恰当的使用乃至滥用，导致细菌耐药性的逐 步上升，为确保这一行之有效的抗菌药物作用靶点继续发挥其良好的治疗效果，研发作用于该靶点的非喹诺酮类抗菌药物来克 服现有的喹诺酮耐药迫在眉睫。 关键词：新型非喹诺酮类拓扑异构酶抑制剂；细菌IIA型拓扑异构酶；抗菌药物 中图分类号：R978.1 文献标志码：A Advances in the research of novel, non-quinolone inhibitors of bacterial type II topoisomerase Cao Gang, Zhao Xi-lin, Xue Yun-xin and Wang Dai (State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen 361102) Abstract Since the invention of the first quinolone-class drug, nalidixic acid, in 1962, four generations and hundreds of new derivatives have been made and bacterial type IIA topoisomerases (DNA gyrase and topoisomerase IV) have been identified as the targets of such antibacterial agents. Previous studies have shown that bacterial DNA replication, which requires the cooperation of DNA gyrase and topoisomerase IV, is a vital process for bacterial growth and survival. The widespread clinical applications and huge success of type IIA topoisomerase-targeting agents in the past 50 years have also demonstrated the clinical relevance of this class of antimicrobials. However, misuse and over- use of the quinolone-based compounds have led to a steady increase in bacterial resistance. To preserve the usefulness of this proven target for treatment efficacy, development of nove