| Synthesis, in vitro anti-breast cancer activity, and intracellular decomposition of amino acid methyl ester and alkyl amide phosphoramidate monoesters of 3'-azido-3'-deoxythymidine (AZT). | |
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MedLine Citation:
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PMID: 10841805 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We report the synthesis and anticancer activity of a series of AZT phosphoramidate monoesters containing amino acid methyl ester (3a-11a) and N-alkyl amide (3b-11b, 9c-9f) moieties. The aromatic amino acid methyl esters were found to be more cytotoxic than the aliphatic analogues toward MCF-7 cells (human pleural effusion breast adenocarcinoma cell line). A marked stereochemical preference for the L-amino acid stereochemistry was also observed in MCF-7 cells. There was no consistent enhancement of cytotoxicity of the methyl amides over the corresponding methyl esters. AZT and the two AZT aromatic amino acid methyl ester phosphoramidates 8a and 9a were found to be more cytotoxic toward MCF-7 cells than to CEM cells (human T-cell lymphoblastic leukemia). The selective cytotoxicity toward MCF-7 cells may be associated with greater intracellular levels of phosphoramidate monoester and/or phosphorylated AZT. |
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Authors:
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V V Iyer; G W Griesgraber; M R Radmer; E J McIntee; C R Wagner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 43 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2000 Jun |
Date Detail:
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Created Date: 2000-07-07 Completed Date: 2000-07-07 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2266-74 Citation Subset: IM; X |
Affiliation:
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Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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chemical synthesis,
chemistry*,
pharmacology Breast Neoplasms / drug therapy* Drug Screening Assays, Antitumor Esters Female Humans Tumor Cells, Cultured Zidovudine / analogs & derivatives*, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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CA61908/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Esters; 30516-87-1/Zidovudine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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