Antiparasitic lethality of sulfonamidebenzamides in kinetoplastids.
Antiparasitic lethality of sulfonamidebenzamides in kinetoplastids.
复制标题
磺酰胺苯甲酰胺在动质体中的抗寄生虫致死作用。
DOI：
10.1016/j.bmcl.2017.01.043
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发表时间：
2017
影响因子：
2.7
通讯作者：
Golden,JenniferE
中科院分区：
文献类型：
--
作者：
Hackler,Amber;Patrick,StephenL;Kahney,ElizabethW;Flaherty,DanielP;Sharlow,ElizabethR;Morris,JamesC;Golden,JenniferE
A sulfonamidebenzamide series was assessed for anti-kinetoplastid parasite activity based on structural similarity to the antiparasitic drug, nifurtimox. Through structure-activity optimization, derivatives with limited mammalian cell toxicity and increased potency toward African trypanosomes and Leishmania promastigotes were developed. Compound22had the best potency against the trypanosome (EC50= 0.010 μM) while several compounds showed ∼10-fold less potency againstLeishmaniapromastigotes without impacting mammalian cells (EC50> 25 μM). While the chemotype originated from an unrelated optimization program aimed at selectively activating an apoptotic pathway in mammalian cancer cells, our preliminary results suggest that a distinct mechanism of action from that observed in mammalian cells is responsible for the promising activity observed in parasites.
