Antibacterial nicotinamide adenine dinucleotide synthetase inhibitors: amide- and ether-linked tethered dimers with alpha-amino acid end groups.
Tethered dimers incorporating natural alpha-amino acid end groups were synthesized, including examples in which the previously reported esterase-sensitive ester linker was replaced with more stable amide or ether linkers. These compounds remained effective both as inhibitors of NAD synthetase and as potent antibacterial agents for Gram-positive strains. Studies on nonspecific effects, including detergent properties and promiscuous inhibition, suggested little contribution to observed activities.
Velu
Sadanandan E
SE
Department of Chemistry, Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, 901 14th Street South, Birmingham, Alabama 35294, USA.
Mou
Liyuan
L
Luan
Chi-Hao
CH
Yang
Zhengrong W
ZW
DeLucas
Lawrence J
LJ
Brouillette
Christie G
CG
Brouillette
Wayne J
WJ
D019732:Amide Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001412:Bacillus subtilis / Q000201:enzymology; D003902:Detergents / Q000737:chemistry; D019281:Dimerization; D004987:Ethers / Q000737:chemistry; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009243:NAD / Q000378:metabolism*; D017830:Octoxynol / Q000737:chemistry; D013329:Structure-Activity Relationship
D000577:Amides; D000596:Amino Acids; D000900:Anti-Bacterial Agents; D003902:Detergents; D004987:Ethers; D009243:NAD; D017830:Octoxynol; D019732:Amide Synthases; C038479:NAD+ synthase