7-Alkyl-N2-substituted-3-deazaguanines. Synthesis, DNA polymerase III inhibition and antibacterial activity
| Autor: | Michelle M. Butler, Joseph Gambino, Neal C. Brown, Sofya Dvoskin, Zheng-yu Long, George E. Wright, Marjorie H. Barnes, Wei-Chu Xu, Chengxin Zhi |
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| Rok vydání: | 2011 |
| Předmět: |
Guanine
Gram-positive bacteria Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Gram-Positive Bacteria medicine.disease_cause Biochemistry Article Mice Drug Discovery Escherichia coli medicine Animals Enzyme Inhibitors Molecular Biology Polymerase DNA Polymerase III Antibacterial agent chemistry.chemical_classification biology Chemistry Organic Chemistry Staphylococcal Infections biology.organism_classification Anti-Bacterial Agents Enzyme Enzyme inhibitor biology.protein Molecular Medicine DNA Polymerase Inhibitor Bacteria |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:4197-4202 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2011.05.093 |
| Popis: | Several 2-anilino- and 2-benzylamino-3-deaza-6-oxopurines [3-deazaguanines] and selected 8-methyl and 8-aza analogs have been synthesized. 7-Substituted N2-(3-ethyl-4-methylphenyl)-3-deazaguanines were potent and selective inhibitors of Gram+ bacterial DNA polymerase (pol) IIIC, and 7-substituted N2-(3,4-dichlorobenzyl)-3-deazaguanines were potent inhibitors of both pol IIIC and pol IIIE from Gram+ bacteria, but weakly inhibited pol IIIE from Gram− bacteria. Potent enzyme inhibitors in both classes inhibited the growth of Gram+ bacteria (MICs 2.5–10 μg/ml), and were inactive against the Gram− organism Escherichia coli. Several derivatives had moderate protective activity in Staphylococcus aureus-infected mice. |
| Databáze: | OpenAIRE |
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