Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis.
The chemical synthesis of 4-phenoxybenzamide adenine dinucleotide (3), a NAD analogue which mimics isoniazid-NAD adduct and inhibits Mycobacterium tuberculosis NAD-dependent enoyl-ACP reductase (InhA), is reported. The 4-phenoxy benzamide riboside (1) has been prepared as a key intermediate, converted into its 5'-mononucleotide (2), and coupled with AMP imidazolide to give the desired NAD analogue 3. It inhibits InhA with IC50 = 27 microM.
Bonnac
Laurent
L
Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA.
Gao
Guang-Yao
GY
Chen
Liqiang
L
Felczak
Krzysztof
K
Bennett
Eric M
EM
Xu
Hua
H
Kim
TaeSoo
T
Liu
Nina
N
Oh
HyeWon
H
Tonge
Peter J
PJ
Pankiewicz
Krzysztof W
KW
D000227:Adenine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009243:NAD / Q000031:analogs & derivatives* / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000227:Adenine Nucleotides; D009243:NAD; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)