title: Discovery and Optimization of NAD+-Dependent DNA Ligase Inhibitors as Novel Antibacterial Compounds.
abstract: With the serious problem of multiple drug resistance to antibiotics among pathogenic bacteria spreading across the world over the past 30 years, it is crucial to search for novel inhibitors with distinct modes of action from diverse chemical classes. NAD+-dependent DNA ligases (LigAs) are essential enzymes in bacteria, vital for DNA replication and repair. Additionally, LigAs exclusively exist in eubacteria and some viruses and are not found in humans. Those enzymes have therefore been identified as attractive antibacterial drug targets. In this review we explore the discovered inhibitors of LigA through high-throughput screening or virtual screening respectively and their further structure optimization.
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, China.
authors: Fangchao
authors: F
authors: Bi
authors: The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors: Ruixin
authors: R
authors: Ma
authors: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan 250012, China.
authors: Shutao
authors: S
authors: Ma
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D011088:DNA Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009243:NAD; D011088:DNA Ligases
keywords: DNA ligases; HTS; LigAs; VS.; antibacterial; inhibitors