Isosteric analogues of nicotinamide adenine dinucleotide derived from furanfurin, thiophenfurin, and selenophenfurin as mammalian inosine monophosphate dehydrogenase (type I and II) inhibitors
| Autor: | Mario Grifantini, Loredana Cappellacci, Eliezer Huberman, Palmarisa Franchetti, Paolo Perlini, Adrian Butler, Bryan P. Schneider, Frank R. Collart, Hiremagalur N. Jayaram |
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| Rok vydání: | 1998 |
| Předmět: |
Ribonucleotide
Stereochemistry Nicotinamide adenine dinucleotide Isozyme chemistry.chemical_compound IMP Dehydrogenase IMP dehydrogenase Organoselenium Compounds Drug Discovery medicine Humans Enzyme Inhibitors chemistry.chemical_classification biology NAD Recombinant Proteins Kinetics Enzyme chemistry Biochemistry Enzyme inhibitor biology.protein Molecular Medicine NAD+ kinase Ribonucleosides Tiazofurin medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 41(10) |
| ISSN: | 0022-2623 |
| Popis: | Dinucleotides TFAD (6), FFAD (7), and SFAD (8), isosteric NAD analogues derived, respectively, from C-nucleosides 5-beta-d-ribofuranosylthiophene-3-carboxamide (thiophenfurin, 1), 5-beta-d-ribofuranosylfuran-3-carboxamide (furanfurin, 2), and 5-beta-d-ribofuranosylselenophene-3-carboxamide (selenophenfurin, 5), were synthesized as human inosine monophosphate dehydrogenase (IMPDH) type I and II inhibitors. The synthesis was carried out by imidazole-catalyzed coupling of the 5'-monophosphate of 1, 2, and 5 with AMP. These dinucleotides, which are also analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) and selenazole-4-carboxamide adenine dinucleotide (SAD), the active metabolites of the oncolytic C-nucleosides 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) and 2-beta-D-ribofuranosylselenazole-4-carboxamide (selenazofurin), were evaluated for their inhibitory potency against recombinant human IMPDH type I and II. The order of inhibitory potency found was SAD > SFAD = TFAD = TAD >> FFAD for both enzyme isoforms. No significant difference was found in inhibition of IMPDH type I and II. |
| Databáze: | OpenAIRE |
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