Synthesis and evaluation of analogues of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine as inhibitors of tumor cell growth, trypanosomal growth, and HIV-1 infectivity.

Abstract	A well-defined series of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine analogues was designed and synthesized in order to further ascertain the optimal structural requirements for S-adenosylmethionine decarboxylase inhibition and potentially to augment and perhaps separate their antiproliferative and antitrypanosomal activities. Most structural modifications had a deleterious affect on both the antitrypanosomal and antineoplastic activity of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine. However, di-O-acetylation of the parent compound produced a potential prodrug that caused markedly pronounced inhibition of trypanosomal and neoplastic cell growth and viability. Moreover, the acetylated derivative of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine did inhibit HIV-1 growth and infectivity, whereas the parent compound did not.
Authors	Canio J Marasco Jr, Debora L Kramer, John Miller, Carl W Porter, Cyrus J Bacchi, Donna Rattendi, Louis Kucera, Nathan Iyer, Ralph Bernacki, Paula Pera, Janice R Sufrin
Journal	Journal of medicinal chemistry (J Med Chem) Vol. 45 Issue 23 Pg. 5112-22 (Nov 07 2002) ISSN: 0022-2623 [Print] United States
PMID	12408722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Anti-HIV Agents Antineoplastic Agents Deoxyadenosines Trypanocidal Agents MDL 73811 Adenosylmethionine Decarboxylase
Topics	Adenosylmethionine Decarboxylase (antagonists & inhibitors, chemistry) Animals Anti-HIV Agents (chemical synthesis, chemistry, pharmacology) Antineoplastic Agents (chemical synthesis, chemistry, pharmacology) Cell Line Deoxyadenosines (chemical synthesis, chemistry, pharmacology) Drug Screening Assays, Antitumor HIV-1 (drug effects) Humans Male Mice Structure-Activity Relationship Trypanocidal Agents (chemical synthesis, chemistry, pharmacology) Trypanosoma brucei brucei (drug effects) Trypanosoma brucei rhodesiense (drug effects) Trypanosomiasis (drug therapy) Tumor Cells, Cultured

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