Abstract

New nucleoside and nucleotide analogs will be prepared and studies as antiviral and antitumor agents. These compounds will include (1) lipophilic phosphates of allenols derived from nucleic acid bases capable of penetrating the cell membrane (2) nucleoside analogues containing cyclopropane or cyclobutane moiety and (3) analogues of the anti-HIV agent carbovir. Antitumor activity will be studies in vitro and in vivo using murine leukemia L1210 cultures and a number of other tumor systems including solid tumors. Antiviral effects will be investigated in assays with human immunodeficiency virus (HIV), hepatitis B virus (HBV), human cytomegalovirus (HCMV), and herpes simplex 1 virus (HSV-1). Mechanisms of action will be studied with the active analogues. Adenine will be tested as substrates for adenosine deaminase.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032779-15
Application #
2633749
Study Section
AIDS and Related Research Study Section 4 (ARRD)
Program Officer
Beisler, John A
Project Start
1984-07-01
Project End
1998-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
15
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Wayne State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

Chen, Han; Li, Chengwei; Zemlicka, Jiri et al. (2016) Potency and Stereoselectivity of Cyclopropavir Triphosphate Action on Human Cytomegalovirus DNA Polymerase. Antimicrob Agents Chemother 60:4176-82
Gentry, Brian G; Vollmer, Laura E; Hall, Ellie D et al. (2013) Resistance of human cytomegalovirus to cyclopropavir maps to a base pair deletion in the open reading frame of UL97. Antimicrob Agents Chemother 57:4343-8
Gentry, Brian G; Gentry, Sara N; Jackson, Trachette L et al. (2011) Phosphorylation of antiviral and endogenous nucleotides to di- and triphosphates by guanosine monophosphate kinase. Biochem Pharmacol 81:43-9
Gentry, Brian G; Kamil, Jeremy P; Coen, Donald M et al. (2010) Stereoselective phosphorylation of cyclopropavir by pUL97 and competitive inhibition by maribavir. Antimicrob Agents Chemother 54:3093-8
Zhou, Shaoman; Drach, John C; Prichard, Mark N et al. (2009) (Z)- and (E)-2-(1,2-dihydroxyethyl)methylenecyclopropane analogues of 2'-deoxyadenosine and 2'-deoxyguanosine. Synthesis of all stereoisomers, absolute configuration, and antiviral activity. J Med Chem 52:3397-407
Wu, Zhimeng; Drach, John C; Prichard, Mark N et al. (2009) L-valine ester of cyclopropavir: a new antiviral prodrug. Antivir Chem Chemother 20:37-46
Mhaske, Santosh B; Ksebati, Bashar; Prichard, Mark N et al. (2009) Phosphonate analogues of cyclopropavir phosphates and their E-isomers. Synthesis and antiviral activity. Bioorg Med Chem 17:3892-9
Wu, Zhimeng; Zhou, Shaoman; Zemlicka, Jiri (2009) Stereoselective approach to the Z-isomers of methylenecyclopropane analogues of nucleosides: a new synthesis of antiviral synguanol. Nucleosides Nucleotides Nucleic Acids 28:165-74
Li, Chengwei; Gentry, Brian G; Drach, John C et al. (2009) Synthesis and enantioselectivity of cyclopropavir phosphates for cellular GMP kinase. Nucleosides Nucleotides Nucleic Acids 28:795-808
Li, Chengwei; Prichard, Mark N; Korba, Brent E et al. (2008) Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)-cyclopropylidene]methyl}adenine and -guanine. Bioorg Med Chem 16:2148-55

Showing the most recent 10 out of 55 publications