Ribavirin, tiazofurin, and selenazofurin

mononucleotides and nicotinamide adenine dinucleotide analogues. Synthesis, structure, and interactions with IMP dehydrogenase

Gulilat Gebeyehu, Victor E. Marquez, Anne Van Cott, David A. Cooney, James A. Kelley, Hiremagalur N. Jayaram, Gurpreet S. Ahluwalia, Robert L. Dion, Yvonne A. Wilson, David G. Johns

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

A series of dinucleotides, analogous to nicotinamide adenine dinucleotide but containing the five-membered base nucleosides tiazofurin (1a), selenazofurin (1b), ribavirin (2), and AICAR (3) in place of nicotinamide ribonucleoside, were prepared in greater than 50% yield by reacting the corresponding nucleotide imidazolidates (6a-d) with adenosine 5′-monophosphate (AMP). The symmetric dinucleotides of tiazofurin (TTD, 8e) and selenazofurin (SSD, 8f) were also prepared by a similar methodology. These dinucleotides were characterized by 1H NMR and fast atom bombardment MS and were evaluated for their inhibitory potency against a partially purified preparation of tumoral inosine monophosphate dehydrogenase (IMPD) from P388 cells. The order of potency found was SAD (8b) > TAD (8a) ≫ SSD (8f) ≃ TTD (8e) ≃ RAD (8c) ⋙ ZAD (8d). On kinetic analysis none of the dinucleotides produced competitive inhibition of IMPD with NAD as a variable substrate. In addition to their superior IMPD inhibitory activity, SAD and TAD appear to be the only dinucleotides, besides NAD, that are formed naturally by the NAD pyrophosphorylase from P388 lymphoblasts.

Original languageEnglish (US)
Pages (from-to)99-105
Number of pages7
JournalJournal of Medicinal Chemistry
Volume28
Issue number1
StatePublished - 1985
Externally publishedYes

Fingerprint

tiazofurin
IMP Dehydrogenase
Inosine Monophosphate
Ribavirin
NAD
Silver Sulfadiazine
Oxidoreductases
Nicotinamide-Nucleotide Adenylyltransferase
Adenosine Monophosphate
Nucleosides
Adenosine
Nucleotides
Nuclear magnetic resonance
Atoms
Kinetics
Substrates
selenazofurin

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Gebeyehu, G., Marquez, V. E., Van Cott, A., Cooney, D. A., Kelley, J. A., Jayaram, H. N., ... Johns, D. G. (1985). Ribavirin, tiazofurin, and selenazofurin: mononucleotides and nicotinamide adenine dinucleotide analogues. Synthesis, structure, and interactions with IMP dehydrogenase. Journal of Medicinal Chemistry, 28(1), 99-105.

Ribavirin, tiazofurin, and selenazofurin : mononucleotides and nicotinamide adenine dinucleotide analogues. Synthesis, structure, and interactions with IMP dehydrogenase. / Gebeyehu, Gulilat; Marquez, Victor E.; Van Cott, Anne; Cooney, David A.; Kelley, James A.; Jayaram, Hiremagalur N.; Ahluwalia, Gurpreet S.; Dion, Robert L.; Wilson, Yvonne A.; Johns, David G.

In: Journal of Medicinal Chemistry, Vol. 28, No. 1, 1985, p. 99-105.

Research output: Contribution to journalArticle

Gebeyehu, G, Marquez, VE, Van Cott, A, Cooney, DA, Kelley, JA, Jayaram, HN, Ahluwalia, GS, Dion, RL, Wilson, YA & Johns, DG 1985, 'Ribavirin, tiazofurin, and selenazofurin: mononucleotides and nicotinamide adenine dinucleotide analogues. Synthesis, structure, and interactions with IMP dehydrogenase', Journal of Medicinal Chemistry, vol. 28, no. 1, pp. 99-105.
Gebeyehu, Gulilat ; Marquez, Victor E. ; Van Cott, Anne ; Cooney, David A. ; Kelley, James A. ; Jayaram, Hiremagalur N. ; Ahluwalia, Gurpreet S. ; Dion, Robert L. ; Wilson, Yvonne A. ; Johns, David G. / Ribavirin, tiazofurin, and selenazofurin : mononucleotides and nicotinamide adenine dinucleotide analogues. Synthesis, structure, and interactions with IMP dehydrogenase. In: Journal of Medicinal Chemistry. 1985 ; Vol. 28, No. 1. pp. 99-105.
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abstract = "A series of dinucleotides, analogous to nicotinamide adenine dinucleotide but containing the five-membered base nucleosides tiazofurin (1a), selenazofurin (1b), ribavirin (2), and AICAR (3) in place of nicotinamide ribonucleoside, were prepared in greater than 50{\%} yield by reacting the corresponding nucleotide imidazolidates (6a-d) with adenosine 5′-monophosphate (AMP). The symmetric dinucleotides of tiazofurin (TTD, 8e) and selenazofurin (SSD, 8f) were also prepared by a similar methodology. These dinucleotides were characterized by 1H NMR and fast atom bombardment MS and were evaluated for their inhibitory potency against a partially purified preparation of tumoral inosine monophosphate dehydrogenase (IMPD) from P388 cells. The order of potency found was SAD (8b) > TAD (8a) ≫ SSD (8f) ≃ TTD (8e) ≃ RAD (8c) ⋙ ZAD (8d). On kinetic analysis none of the dinucleotides produced competitive inhibition of IMPD with NAD as a variable substrate. In addition to their superior IMPD inhibitory activity, SAD and TAD appear to be the only dinucleotides, besides NAD, that are formed naturally by the NAD pyrophosphorylase from P388 lymphoblasts.",
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T2 - mononucleotides and nicotinamide adenine dinucleotide analogues. Synthesis, structure, and interactions with IMP dehydrogenase

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AU - Marquez, Victor E.

AU - Van Cott, Anne

AU - Cooney, David A.

AU - Kelley, James A.

AU - Jayaram, Hiremagalur N.

AU - Ahluwalia, Gurpreet S.

AU - Dion, Robert L.

AU - Wilson, Yvonne A.

AU - Johns, David G.

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