An evaluation of Minor Groove Binders as anti-Trypanosoma brucei brucei therapeutics.
An evaluation of Minor Groove Binders as anti-Trypanosoma brucei brucei therapeutics.
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DOI：
10.1016/j.ejmech.2016.03.064
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发表时间：
2016-06-30
影响因子：
6.7
通讯作者：
Suckling CJ
中科院分区：
文献类型：
--
作者：
Scott FJ;Khalaf AI;Giordani F;Wong PE;Duffy S;Barrett M;Avery VM;Suckling CJ
一系列的32个结构上不同的MGBs，来自天然产物偏端霉素，进行了评价，对布氏锥虫布氏。已经发现四种化合物具有显著的活性，在纳摩尔范围内，并且代表进一步优化人类和动物非洲锥虫酶的新治疗的命中。此外，SAR表明头基连接部分是生物活性的重要调节剂。荧光MGB在T. B.布鲁塞。N =细胞核; K =动基体;箭头=其他细胞器。条= 10 μm。小沟结合剂（MGB）具有对抗布氏锥虫的活性。已确定5种MGBs为未来研究的先导药物，每种药物的IC 50值均低于40 nM。DNA仍然是锥虫中这些MGBs的可能靶点，类似于细菌的情况。
A series of 32 structurally diverse MGBs, derived from the natural product distamycin, was evaluated for activity against Trypanosoma brucei brucei. Four compounds have been found to possess significant activity, in the nanomolar range, and represent hits for further optimisation towards novel treatments for Human and Animal African Trypanosomiases. Moreover, SAR indicates that the head group linking moiety is a significant modulator of biological activity. Intracellular localisation of fluorescent MGB in the nucleus and kinetoplast of T. b. brucei. N = nucleus; K = kinetoplast; arrow = other organelles. Bar = 10 μm. Minor Groove Binders (MGBs) possess activity against Trypanosma brucei brucei. 5 MGBs have been identified as leads for future investigation, each with IC50 values lower than 40 nM. DNA remains a possible target for these MGBs in trypanosomes, similar to the case for bacteria.