title: [Virtual screening and antibacterial activity of lead compounds targeting to penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa].
abstract: OBJECTIVE
  This study was carried out to obtain lead compounds targeting penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa by virtual screening.
  
  
  METHODS
  UCSF dock 6.5 was used for the virtual screening from a database containing 1.04 million small molecules. Hit compounds with simple structures were synthesized and then evaluated for their antibacterial activities.
  
  
  RESULTS
  Grid score was used for the first round of screening, and 60000 small molecules whose scores lower than -30 kcal/mol were screened out from the database. These molecules were subjected to the second round of screening using amber score. Approximately 200 hit compounds with scores lower than -20 kcal/mol were analyzed and 4 of them were selected as lead compounds and then synthesized. The minimal inhibition concentrations (MICs) of the lead compounds were between 175-275 μg/mL, which were lower than that of Sulfadiazine (500 μg/mL) significantly. Meanwhile, these compounds were effective for both Gram-negative and Gram-positive bacteria.
  
  
  CONCLUSIONS
  The lead compounds had potential to become new antibacterial agents for conquering the drug resistance of P. aeruginosa.
authors.forename: Zhaowu
authors.initials: Z
authors.lastname: Yu
authors.forename: Lihua
authors.initials: L
authors.lastname: Song
authors.forename: Liyan
authors.initials: L
authors.lastname: Tong
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Zheng
authors.forename: Xingwen
authors.initials: X
authors.lastname: Gong
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D046915:Penicillin-Binding Proteins