PMID: 2536930Feb 1, 1989Paper

2-Acetylpyridine 5-[(dimethylamino)thiocarbonyl]-thiocarbonohydrazone (A1110U), a potent inactivator of ribonucleotide reductases of herpes simplex and varicella-zoster viruses and a potentiator of acyclovir

Proceedings of the National Academy of Sciences of the United States of America
T SpectorP A Furman

Abstract

2-Acetylpyridine 5-[(dimethylamino)thiocarbonyl]thiocarbonohydrazone (A1110U) was found to be a potent inactivator of the ribonucleotide reductases (EC 1.17.4.1) encoded by herpes simplex virus types 1 and 2 and by varicella-zoster virus and to be a weaker inactivator of human ribonucleotide reductase. It also markedly potentiated the antiherpetic activity of acyclovir against these viruses in tissue culture. A1110U both decreased the dGTP pool that builds up when infected cells are treated with acyclovir and induced a large increase in the pool of acyclovir triphosphate. The resultant 100-fold increase in the ratio of the concentrations of acyclovir triphosphate to dGTP should facilitate the binding of the fraudulent nucleotide to its target enzyme, herpes virus-encoded DNA polymerase, and could account for the synergy between A1110U and acyclovir. A similar change in the acyclovir triphosphate-to-dGTP ratio was previously reported to be induced by another ribonucleotide reductase inhibitor, 2-acetylpyridine 4-(2-morpholinoethyl)thiosemicarbazone (A723U). However, A1110U is considerably more potent and may have better clinical potential. Synergistic toxic interactions between A1110U and acyclovir were not detected in uninfecte...Continue Reading

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Citations

Nov 1, 1989·Journal of Virological Methods·T Spector, J A Harrington
Oct 1, 1990·Antiviral Research·M N Prichard, C Shipman
Sep 1, 1994·Antiviral Research·J CinatlH W Doerr
Mar 1, 1996·Antiviral Research·M MarchettiL Seganti
Aug 1, 1994·International Journal of Antimicrobial Agents·R SnoeckE De Clercq
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J I Cohen, K E Seidel
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·A MarcelloG Palù
Oct 1, 1989·Antimicrobial Agents and Chemotherapy·M N EllisT Spector
Aug 1, 1989·Antimicrobial Agents and Chemotherapy·D M CoenS K Weller
May 1, 1991·Antimicrobial Agents and Chemotherapy·D R AverettT A Krenitsky
Mar 1, 1993·Antimicrobial Agents and Chemotherapy·M N PrichardC Shipman
Jan 1, 1996·Annual Review of Microbiology·A M Arvin, A A Gershon
Jan 8, 2010·Drug Design, Development and Therapy·Bryan M GebhardtGeorge E Wright
Jan 31, 2003·Expert Opinion on Investigational Drugs·Gerald Kleymann
Jul 19, 2002·Reviews in Medical Virology·Arianna LoregianGiorgio Palù
Mar 3, 2010·The Journal of Pharmacology and Experimental Therapeutics·Takashi KuramotoKimiyasu Shiraki
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Apr 20, 2006·Antiviral Research·Stanislaw F Wnuk, Morris J Robins
Jan 19, 1996·Journal of Medicinal Chemistry·N A Van DraanenG W Koszalka

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