Novel nicotinamide adenine dinucleotide analogues as potential anticancer agents: Quest for specific inhibition of inosine monophosphate dehydrogenase
Novel nicotinamide adenine dinucleotide analogues as potential anticancer agents: Quest for specific inhibition of inosine monophosphate dehydrogenase
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DOI：
10.1016/s0163-7258(97)00092-2
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发表时间：
1997-10-01
影响因子：
13.5
通讯作者：
Pankiewicz, KW
中科院分区：
文献类型：
--
作者：
Pankiewicz, KW
Synthetic nicotinamide adenine dinucleotide (NAD) analogues containing 5-beta-D-ribofuranosylnicotinamide (C-NAD), 6-beta-D-ribofuranosylpicolinamide (C-PAD), 3-beta-D-ribofuranosylbenzamide (BAD), and 2-beta-D-ribofuranosylthiazole-4-carboxamide (TAD) in place of the nicotinamide riboside moiety are described and evaluated as potential inhibitors of inosine monophosphate dehydrogenase (IMPDH). TAD and BAD showed potent inhibitory activity against the enzyme in the form of pyrophosphates, as well as metabolically stable methylene-and difluoromethylenebis(phosphonate)s. Fluorination at the C2' (ribo and arabino configuration) and C3' (ribo) of the adenosine moiety of TAD afforded analogues highly potent against IMPDH, but weakly active against alcohol dehydrogenase. With the exception of the methylenebis(phosphonate) analogue of TAD compounds containing a methylene bridge were poor inhibitors of growth of K562 cells. On the other hand, NAD analogues containing difluoromethylene linkage were highly effective in inhibition of K562 cell growth, as web as potent inducers of K562 cell differentiation. Such compounds, therefore, may be of potential therapeutic interest. (C) 1997 Elsevier Science Inc.
