Anti-trypanosomal activities of DNA topoisomerase inhibitors
Anti-trypanosomal activities of DNA topoisomerase inhibitors
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DOI：
10.1016/j.actatropica.2005.01.005
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发表时间：
2005-03-01
期刊：
影响因子：
2.7
通讯作者：
Steverding, D
中科院分区：
文献类型：
--
作者：
Deterding, A;Dungey, FA;Steverding, D
只有四种药物可用于治疗具有不良毒副作用的非洲昏睡病患者。因此，迫切需要开发新的抗锥虫药物。在这项研究中，15种DNA拓扑异构酶抑制剂，包括批准的抗癌药物，在体外测试了对血流形式的布鲁氏锥虫和人白血病HL-60细胞的活性。所有化合物均具有抗锥虫活性，其ED50值在3 nM~30 mM之间，MIC值在100 nM~100 mU M之间。最有效的DNA拓扑异构酶抑制剂阿克拉阿霉素、阿霉素和米托蒽醌的杀锥虫活性与市售抗锥虫药物相当。这些数据支持将DNA拓扑异构酶抑制剂用作抗锥虫药物开发的先导化合物。(C)2005 Elsevier B.V.保留所有权利。
Only four drugs are available for chemotherapy of human African sleeping sickness with undesirable toxic side effects. The development of new anti-trypanosomal drugs is, therefore, urgently required. In this study, 15 DNA topoisomerase inhibitors, including approved anti-cancer drugs, were tested for in vitro activity against bloodstream forms of Trypanosoma brucei and human leukaernia HL-60 cells. All compounds exhibited anti-trypanosomal activity, with ED50 values ranging between 3 nM and 30 mu M, and MIC values between 100 nM and > 100 mu M. The trypanocidal activities of the most effective DNA topoisomerase inhibitors, aclarubicin, doxorubicin and mitoxantrone, were comparable with those of commercial anti-trypanosomal drugs. These data support the use of DNA topoisomerase inhibitors as lead compounds for anti-trypanosomal drug development. (c) 2005 Elsevier B.V. All rights reserved.