Synthesis, DNA binding and antileishmanial activity of low molecular weight bis-arylimidamides.
Synthesis, DNA binding and antileishmanial activity of low molecular weight bis-arylimidamides.
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DOI：
10.1016/j.ejmech.2012.06.058
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发表时间：
2012-09
影响因子：
6.7
通讯作者：
Boykin DW
中科院分区：
文献类型：
--
作者：
Banerjee M;Farahat AA;Kumar A;Wenzler T;Brun R;Munde MM;Wilson WD;Zhu X;Werbovetz KA;Boykin DW
本文报道了降低抗利什曼原虫化合物DB 766的分子量对DNA结合亲和力、抗利什曼原虫活性和细胞毒性的影响。通过S-（2-萘甲基）硫代亚氨酸芳基酯与相应的胺的偶联反应，合成了双芳基亚酰胺。具体地，我们已经制备了新的系列的双-芳基酰亚胺酰胺，包括3a，3b，6，9a，9 b，9 c，13和18。三种化合物9a、9 c和18以与DB 766相似或适度较低的亲和力结合DNA，这些化合物的其余部分显示出与DNA的相当弱的结合或根本不结合。化合物9a、9 c和13对L. amazonensis的IC 50值小于1 µM，因此针对细胞内L. donovani显示出突出的活性，IC 50值为25-79 nM。尽管这三种化合物的体外细胞毒性很小，但对小鼠毒性很大。
The effects of reducing the molecular weight of the antileishmanial compound DB766 on DNA binding affinity, antileishmanial activity and cytotoxicity are reported. The bis-arylimidamides were prepared by the coupling of aryl S-(2-naphthylmethyl)thioimidates with the corresponding amines. Specifically, we have prepared new series of bis-arylimidamides which include 3a, 3b, 6, 9a, 9b, 9c, 13, and 18. Three compounds 9a, 9c, and 18 bind to DNA with similar or moderately lower affinity to that of DB766, the rest of these compounds either show quite weak binding or no binding at all to DNA. Compounds 9a, 9c, and 13 were the most active against L. amazonensis showing IC50 values of less than 1 µM, so they were screened against intracellular L. donovani showing outstanding activity with IC50.values of 25–79 nM. Despite exhibiting little in vitro cytotoxicity these three compounds were quite toxic to mice.
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影响因子：
3.5
作者：
Delfin, Dawn A.;Morgan, Rachel E.;Werbovetz, Karl A.
通讯作者：
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影响因子：
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