Discovery of selective menaquinone biosynthesis inhibitors against Mycobacterium tuberculosis.
Discovery of selective menaquinone biosynthesis inhibitors against Mycobacterium tuberculosis.
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DOI：
10.1021/jm201608g
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发表时间：
2012-04-26
影响因子：
7.3
通讯作者：
Kurosu, Michio
中科院分区：
文献类型：
--
作者：
Debnath, Joy;Siricilla, Shajila;Wan, Bajoie;Crick, Dean C.;Lenaerts, Anne J.;Franzblau, Scott G.;Kurosu, Michio
Aurachin RE（1）是一种具有MenA（1，4-dihydroxy-2-naphthoate prenyltransferase）和细菌电子传递抑制活性的抗生素。Aurachin RE是一系列Aurachin天然产物中唯一在C9′-位烷基侧链上具有手性中心的分子。为了鉴定针对结核分枝杆菌的选择性MenA抑制剂，基于先前鉴定的MenA抑制剂和1.合成的分子在包括MenA酶和细菌生长抑制测定的体外测定中进行评价。我们可以鉴定新型MenA抑制剂，其显示出杀死非复制型M.在低氧恢复试验（LORA）中，即使在高浓度下，也不会抑制其他革兰氏阳性细菌的生长。本文报道的MenA抑制剂是用于开发对非复制型M具有强活性的选择性抗分枝杆菌剂的有用的新药效团。结核
Aurachin RE (1) is a strong antibiotic that was recently found to possess MenA (1,4-dihydroxy-2-naphthoate prenyltransferase) and bacterial electron transport inhibitory activities. Aurachin RE is the only molecule in a series of aurachin natural products that has the chiral center in the alkyl side chain at C9′-position. To identify selective MenA inhibitors against Mycobacterium tuberculosis, a series of chiral molecules were designed based on the structures of previously identified MenA inhibitors and 1. The synthesized molecules were evaluated in in vitro assays including MenA enzyme and bacterial growth inhibitory assays. We could identify novel MenA inhibitors that showed significant increase in potency of killing non-replicating M. tuberculosis in the low oxygen recovery assay (LORA) without inhibiting other Gram-positive bacterial growth even at high concentrations. The MenA inhibitors reported here are useful new pharmacophores for the development of selective antimycobacterial agents with strong activity against non-replicating M. tuberculosis.
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影响因子：
7.3
作者：
Kurosu, Michio;Narayanasamy, Prabagaran;Crick, Dean C.
通讯作者：
Crick, Dean C.
影响因子：
4.9
作者：
Lenaerts, AJ;Gruppo, V;Orme, IM
通讯作者：
Orme, IM
影响因子：
3.3
作者：
Kitagawa, Wataru;Tamura, Tomohiro
通讯作者：
Tamura, Tomohiro
DOI：
10.3390/molecules15031531
发表时间：
2010-03-10
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Kurosu M;Begari E
通讯作者：
Begari E
影响因子：
56.9
作者：
Andries, K;Verhasselt, P;Jarlier, V
通讯作者：
Jarlier, V