Virtual screening to identify lead inhibitors for bacterial NAD synthetase (NADs).
Virtual screening was employed to identify new drug-like inhibitors of NAD synthetase (NADs) as antibacterial agents. Four databases of commercially available compounds were docked against three subsites of the NADs active site using FlexX in conjunction with CScore. Over 200 commercial compounds were purchased and evaluated in enzyme inhibition and antibacterial assays. 18 compounds inhibited NADs at or below 100 microM (7.6% hit rate), and two were selected for future SAR studies.
Moro
Whitney Beysselance
WB
Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, 1025 18th Street South, Birmingham, AL 35294, United States.
Yang
Zhengrong
Z
Kane
Tasha A
TA
Brouillette
Christie G
CG
Brouillette
Wayne J
WJ
D019732:Amide Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D012984:Software
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D019732:Amide Synthases; C038479:NAD+ synthase