Portal de Periódicos da CAPES

Small molecule inhibitors of E. coli primase, a novel bacterial target

2007; Elsevier BV; Volume: 17; Issue: 10 Linguagem: Inglês

10.1016/j.bmcl.2007.02.056

1464-3405

Atul Agarwal, Shirley Louise‐May, Jane A. Thanassi, Steven D. Podos, Jijun Cheng, Christy L. Thoma, Cuixian Liu, Jason A. Wiles, David M. Nelson, Avinash Phadke, Barton J. Bradbury, Milind Deshpande, Michael J. Pucci,

DNA Repair Mechanisms

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.