Acyclic sugar analogs of triciribine: lack of antiviral and antiproliferative activity correlate with low intracellular phosphorylation.
Triciribine and triciribine monophosphate have antiviral and antiproliferative activity at low or submicromolar concentrations. In an effort to improve and better understand this activity, we have synthesized a series of acyclic analogs and evaluated them for activity against select viruses and cancer cell lines. We conclude that the rigid ribosyl ring system of triciribine must be intact in order to be phosphorylated and to obtain significant antiviral and antiproliferative activity.
Porcari
A R
AR
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
Borysko
K Z
KZ
Ptak
R G
RG
Breitenbach
J M
JM
Wotring
L L
LL
Drach
J C
JC
Townsend
L B
LB
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003587:Cytomegalovirus / Q000187:drug effects; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D010766:Phosphorylation; D012263:Ribonucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012266:Ribose / Q000737:chemistry; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010948:Viral Plaque Assay
D019380:Anti-HIV Agents; D000964:Antimetabolites, Antineoplastic; D000998:Antiviral Agents; D006131:Growth Inhibitors; D012263:Ribonucleosides; C023764:triciribine; D012266:Ribose