Selective Inhibition of Bacterial Topoisomerase I by alkynyl-bisbenzimidazoles.
Selective Inhibition of Bacterial Topoisomerase I by alkynyl-bisbenzimidazoles.
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DOI：
10.1039/c4md00140k
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发表时间：
2014-06-01
期刊：
影响因子：
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通讯作者：
Arya DP
中科院分区：
文献类型：
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作者：
Ranjan N;Fulcrand G;King A;Brown J;Jiang X;Leng F;Arya DP
Hoechst染料是众所周知的DNA结合剂，其非选择性地抑制哺乳动物拓扑异构酶I和II的功能。在此，我们表明，Hoechst 33258为基础的双苯并咪唑（DPA 151-154），含有一个末端炔，是有效的和选择性的抑制剂E。杆菌拓扑异构酶I这些双苯并咪唑显示出比Hoechst 33342或Hoechst 33258更好的拓扑异构酶I抑制作用，IC 50值在2.47-6.63 μM范围内。双苯并咪唑类化合物DPA 151-154对大肠杆菌也有选择性抑制作用。杆菌拓扑异构酶I优于DNA促旋酶和人拓扑异构酶I和II，并有效抑制细菌生长。
Hoechst dyes are well known DNA binders that non-selectively inhibit the function of mammalian topoisomerase I and II. Herein, we show that Hoechst 33258 based bisbenzimidazoles (DPA 151–154), containing a terminal alkyne, are effective and selective inhibitors of E. coli. topoisomerase I. These bisbenzimidazoles displayed topoisomerase I inhibition much better than Hoechst 33342 or Hoechst 33258 with IC50 values in the range of 2.47–6.63 μM. Bisbenzimidazoles DPA 151-154 also display selective inhibition of E. coli. topoisomerase I over DNA gyrase and Human topoisomerases I and II, and effectively inhibit bacterial growth.