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TitleAntineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs
Publication TypeJournal Article
Year of Publication2012
AuthorsPettit, G.R., Rosenberg H.J., Dixon R., Knight J.C., Hamel E., Chapuis J.-C., Pettit R.K., Hogan F., Sumner B., Ain K.B., and Trickey-Platt B.
JournalJournal of Natural Products
Pagination385 - 393
Date Published2012
ISSN01633864 (ISSN)
Keywords3 iodo 4,4',5 trimethoxy 3' hydroxystilbene, 3,5 diiodo 4,4, dimethoxy 3' hydroxystilbene, animal cell, Animals, antineoplastic activity, antineoplastic agent, Antineoplastic Agents, article, Child, controlled study, diiodocombstatin phosphate derivative, drug effect, Drug Screening Assays, Antitumor, drug structure, drug synthesis, Female, human, human cell, Human Umbilical Vein Endothelial Cells, Humans, Hydrocarbons, Iodinated, iodocombstatin phosphate derivative, Male, Mice, Microbial Sensitivity Tests, Molecular Structure, mouse, Murinae, nonhuman, Organophosphorus Compounds, potassium 3,5 diiodo 4,4' dimethoxystilbene 3' o phosphate, prodrug, Prodrugs, Stilbenes, structure analysis, unclassified drug
AbstractToward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted. © 2012 The American Chemical Society and American Society of Pharmacognosy.

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