Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.
Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.
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DOI：
10.1016/j.bmc.2014.03.035
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发表时间：
2014-05-01
影响因子：
3.5
通讯作者：
Ojima I
中科院分区：
文献类型：
--
作者：
Park B;Awasthi D;Chowdhury SR;Melief EH;Kumar K;Knudson SE;Slayden RA;Ojima I
丝状温度敏感蛋白Z（FtsZ）是一种细胞分裂必需蛋白，是新一代抗菌药物开发的重要靶点。作为苯并咪唑类化合物构效关系研究的一部分，我们合成了376个新的2，5，6-三取代苯并咪唑类化合物，这些化合物在6位带有醚或硫醚键。在针对Mtb H37 Rv的初步HTP筛选中，在5 μg/mL的截止浓度下，108种化合物被鉴定为命中物。在这些命中中，10种化合物表现出在0.63-12.5 μg/mL范围内的MIC值。用最有效的化合物5a进行的光散射测定和TEM分析清楚地表明其分子靶标是Mtb-FtsZ。此外，测定了5a与Mtb-FtsZ的Kd为1.32 μM。
Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63–12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM.
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影响因子：
3.2
作者：
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通讯作者：
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影响因子：
2.8
作者：
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影响因子：
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