title: 3D-QSAR and molecular docking for the discovery of ketolide derivatives.
abstract: BACKGROUND
  There is an urgent need to discover novel antibiotics to overcome the growing problem of antibiotic resistance, which has become a serious concern in current medicine. Ketolides, the third generation of macrolide antibiotics, have shown promising effect against macrolide-resistant pathogens in respiratory diseases. Currently, a number of ketolide derivatives with excellent antibacterial activities have been reported, while their structure-activity relationships (SARs) were rarely explored systematically. Computer-aided drug design (CADD) such as 3D-QSAR and molecular docking are useful tools to study drug SARs in medicinal chemistry. Using these technologies, ketolide derivatives were systemically analyzed revealing important useful information about their SARs, providing useful information which can guide new drug design and optimization.
  
  
  METHODS
  The authors provide an overview of the currently reported 3D-QSAR models of ketolide derivatives. The authors present a comprehensive SAR model obtained from in-depth 3D-QSAR and molecular docking analysis for all kinds of ketolide derivatives.
  
  
  CONCLUSIONS
  3D-QSAR has been shown to be a reliable tool that had successfully assisted the design of several new antibiotics with improved activity and reduced toxicity. By applying 3D-QSAR and molecular docking, a comprehensive and systematic SAR model for ketolide derivative discovery was formed, which is important to guide future drug design for the discovery of better ketolides with lower toxicity.
authors: Jinan University, College of Pharmacy, Department of Medicinal Chemistry, Guangzhou, P.R. China.
authors: Zhi-Xiong
authors: ZX
authors: Ruan
authors: De-Sheng
authors: DS
authors: Huangfu
authors: Xing-Jun
authors: XJ
authors: Xu
authors: Ping-Hua
authors: PH
authors: Sun
authors: Wei-Min
authors: WM
authors: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017076:Computer-Aided Design; D015195:Drug Design; D004352:Drug Resistance, Microbial / Q000187:drug effects; D006801:Humans; D048628:Ketolides / Q000494:pharmacology*; D008962:Models, Theoretical; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides