Isosteric analogues of nicotinamide adenine dinucleotide derived from furanfurin, thiophenfurin, and selenophenfurin as mammalian inosine monophosphate dehydrogenase (type I and II) inhibitors

Palmarisa Franchetti, Loredana Cappellacci, Paolo Perlini, Hiremagalur N. Jayaram, Adrian Butler, Bryan Schneider, Frank R. Collart, Eliezer Huberman, Mario Grifantini

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Dinucleotides TFAD (6), FFAD (7), and SFAD (8), isosteric NAD analogues derived, respectively, from C-nucleosides 5-β-D-ribofuranosylthiophene-3- carboxamide (thiophenfurin, 1), 5-β-Dribofuranosylfuran-3-carboxamide (furanfurin, 2), and 5-β-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-4carboxamide adenine dinucleotide (SAD), the active metabolites of the oncolytic C-nucleosides 2-β-D- ribofuranosylthiazole-4-carboxamide (tiazofurin) and 2-β-D- ribofuranosylselenazole-4carboxamide (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.

Original languageEnglish
Pages (from-to)1702-1707
Number of pages6
JournalJournal of Medicinal Chemistry
Volume41
Issue number10
DOIs
StatePublished - May 7 1998

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tiazofurin
Inosine Monophosphate
Adenine
Nucleosides
NAD
Oxidoreductases
Adenosine Monophosphate
Protein Isoforms
Metabolites
Enzymes
thiazole-4-carboxamide adenine dinucleotide
human IMPDH2 protein
selenophenfurin
furanfurin
thiophenfurin

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Isosteric analogues of nicotinamide adenine dinucleotide derived from furanfurin, thiophenfurin, and selenophenfurin as mammalian inosine monophosphate dehydrogenase (type I and II) inhibitors. / Franchetti, Palmarisa; Cappellacci, Loredana; Perlini, Paolo; Jayaram, Hiremagalur N.; Butler, Adrian; Schneider, Bryan; Collart, Frank R.; Huberman, Eliezer; Grifantini, Mario.

In: Journal of Medicinal Chemistry, Vol. 41, No. 10, 07.05.1998, p. 1702-1707.

Research output: Contribution to journalArticle

Franchetti, Palmarisa ; Cappellacci, Loredana ; Perlini, Paolo ; Jayaram, Hiremagalur N. ; Butler, Adrian ; Schneider, Bryan ; Collart, Frank R. ; Huberman, Eliezer ; Grifantini, Mario. / Isosteric analogues of nicotinamide adenine dinucleotide derived from furanfurin, thiophenfurin, and selenophenfurin as mammalian inosine monophosphate dehydrogenase (type I and II) inhibitors. In: Journal of Medicinal Chemistry. 1998 ; Vol. 41, No. 10. pp. 1702-1707.
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abstract = "Dinucleotides TFAD (6), FFAD (7), and SFAD (8), isosteric NAD analogues derived, respectively, from C-nucleosides 5-β-D-ribofuranosylthiophene-3- carboxamide (thiophenfurin, 1), 5-β-Dribofuranosylfuran-3-carboxamide (furanfurin, 2), and 5-β-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-4carboxamide adenine dinucleotide (SAD), the active metabolites of the oncolytic C-nucleosides 2-β-D- ribofuranosylthiazole-4-carboxamide (tiazofurin) and 2-β-D- ribofuranosylselenazole-4carboxamide (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.",
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AU - Cappellacci, Loredana

AU - Perlini, Paolo

AU - Jayaram, Hiremagalur N.

AU - Butler, Adrian

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AU - Collart, Frank R.

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