Author/Authors :
Laurent Bonnac، نويسنده , , Guangyao Gao، نويسنده , , Liqiang Chen، نويسنده , , Krzysztof Felczak، نويسنده , , Eric M. Bennett، نويسنده , , Hua Xu، نويسنده , , TaeSoo Kim، نويسنده , , Nina Liu، نويسنده , , HyeWon Oh، نويسنده , , Peter J. Tonge، نويسنده , , Krzysztof W. Pankiewicz، نويسنده ,
Abstract :
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 μM.
Keywords :
M. tuberculosis , NAD analogues , Enoyl-ACP reductase (InhA) , Isoniazid , Fragment-based drug discovery
