Leishmania panamensis:: Comparative inhibition of nuclear DNA topoisomerase II enzymes from promastigotes and human macrophages reveals anti-parasite selectivity of fluoroquinolones, flavonoids and pentamidine
Leishmania panamensis:: Comparative inhibition of nuclear DNA topoisomerase II enzymes from promastigotes and human macrophages reveals anti-parasite selectivity of fluoroquinolones, flavonoids and pentamidine
复制标题
DOI：
10.1016/j.exppara.2007.02.018
复制
发表时间：
2007-08-01
影响因子：
2.1
通讯作者：
Walker, John
中科院分区：
文献类型：
--
作者：
Cortazar, Tania M.;Coombs, Graham H.;Walker, John
某些模型抑制剂对巴拿马利什曼原虫前体核DNA拓扑异构酶II （TOPII）的催化活性具有选择性作用。与人巨噬细胞酶相比，第二代氟喹诺酮类依诺沙星和环丙沙星具有非常高的抗寄生虫选择性，对L. panamensis TOPII的效力分别提高了582倍和40倍。黄酮类、槲皮素和鞣花酸对巴拿马乳杆菌TOPII的抑制作用为161倍，对巨噬细胞TOPII的抑制作用为15.7倍。原小檗碱是利什曼原虫和巨噬细胞TOPII的有效抑制剂。双苯并咪唑类药物和乙酰二胺类药物对寄生虫和宿主TOPII表现出一致的高效力，但第二种二胺类戊脒对利什曼原虫TOPII的特异性高17.6倍。锑酸钠对寄生虫TOPII无效，对巨噬细胞酶的效力高4.3倍。这些发现表明，某些氟喹诺酮类药物和喷他脒的杀利什曼尼虫活性可能部分通过抑制TOPII介导。(c) 2007爱思唯尔公司版权所有。
Certain model inhibitors exerted selective action against the catalytic activity of nuclear DNA topoisomerase II (TOPII) of Leishmania panamensis promastigotes. The second-generation fluoroquinolones enoxacin and ciprofloxacin exhibited extraordinarily high anti-parasite selectivity displaying 582- and 40-fold greater potencies against L. panamensis TOPII as compared with the human macrophage enzyme. The flavonoids quercetin and ellagic acid showed inverse specificities, the former being 161-fold more potent against L. panamensis TOPII, and the latter 15.7-fold more active against macrophage TOPII. The protoberberine coralyne was a potent inhibitor of both Leishmania and macrophage TOPII. Bis-benzimidazoles and the diamidine diminazene aceturate exhibited uniformly high potencies against parasite and host TOPII, but a second diamidine pentamidine showed 17.6-fold greater specificity for Leishmania TOPII The antimonial sodium stibogluconate was an ineffective inhibitor of parasite TOPII showing 4.3-fold greater potency against the macrophage enzyme. These findings suggest that the leishmanicidal activities of certain fluoroquinolones and pentamidine may be mediated partly through TOPII inhibition. (c) 2007 Elsevier Inc. All rights reserved.