Discovery of bacterial NAD+-dependent DNA ligase inhibitors: optimization of antibacterial activity

Autor:	Madhusudhan Reddy Gowravaram, Shannon X. Zhao, Robert Albert, George B. Mullen, Jenna Harang, Marta Cavero-Tomas, Scott D. Mills, Suzanne Stokes, Brendan Chen, Ce-Feng Liu, Hoan Huynh, Min Lu, James T. Loch
Rok vydání:	2011
Předmět:	Staphylococcus aureus Adenosine DNA Ligases Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Microbial Sensitivity Tests medicine.disease_cause Crystallography X-Ray Biochemistry chemistry.chemical_compound Drug Discovery Ribose Streptococcus pneumoniae medicine Binding site Enzyme Inhibitors Molecular Biology chemistry.chemical_classification DNA ligase Binding Sites Chemistry Organic Chemistry NAD Anti-Bacterial Agents Protein Structure Tertiary Molecular Medicine NAD+ kinase Antibacterial activity medicine.drug
Zdroj:	Bioorganicmedicinal chemistry letters. 21(15)
ISSN:	1464-3405
Popis:	Optimization of adenosine analog inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. Antibacterial activity against Streptococcus pneumoniae and Staphylococcus aureus was improved by modification of the 2-position substituent on the adenine ring and 3'- and 5'-substituents on the ribose. Compounds with logD values 1.5-2.5 maximized potency and maintained drug-like physical properties.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc4ee6f3599f3d60296bda6b3a7eeb77 https://pubmed.ncbi.nlm.nih.gov/21719282 Zobrazit plný text záznamu Full Text from ScienceDirect