Small molecule inhibitors of E-coli primase, a novel bacterial target
Small molecule inhibitors of E-coli primase, a novel bacterial target
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DOI：
10.1016/j.bmcl.2007.02.056
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发表时间：
2007-05-15
影响因子：
2.7
通讯作者：
Pucci, Michael J.
中科院分区：
文献类型：
--
作者：
Agarwal, Atul;Louise-May, Shirley;Pucci, Michael J.
细菌引物酶对于革兰氏阳性和革兰氏阴性细菌中的 DNA 复制至关重要。它在结构上也与真核引物酶不同，因此是一个有吸引力但尚未充分探索的治疗干预靶标。我们应用虚拟筛选来发现引物酶抑制剂，随后这些初始命中的几种市售类似物显示出有效的引物酶抑制和体外抗菌活性。这项工作提供了引物酶配体的 3D 药效团、SAR 趋势和可进一步优化的先导化合物。 (c) 2007 Elsevier Ltd. 保留所有权利。
Bacterial primase is essential for DNA replication in Gram-positive and Gram-negative bacteria. It is also structurally distinct from eukaryotic primases, and therefore an attractive, but under-explored, target for therapeutic intervention. We applied virtual screening to discover primase inhibitors, and subsequently several commercially available analogs of these initial hits showed potent primase inhibition and in vitro antibacterial activity. This work provides a 3D pharmacophore for primase ligands, SAR trends, and leads that can be further optimized. (c) 2007 Elsevier Ltd. All rights reserved.