Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs

George Pettit, Heidi J. Rosenberg, Rachel Dixon, John C. Knight, Ernest Hamel, Jean Chapuis, Robin Pettit, Fiona Hogan, Brandy Sumner, Kenneth B. Ain, Brindi Trickey-Platt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Toward 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.

Original languageEnglish (US)
Pages (from-to)385-393
Number of pages9
JournalJournal of Natural Products
Volume75
Issue number3
DOIs
StatePublished - Mar 23 2012

Fingerprint

Prodrugs
Antineoplastic Agents
Phosphates
Cells
Cell Line
Growth
Lymphoid Leukemia
Pediatrics
Angiogenesis Inhibitors
Tubulin
Neuroblastoma
Thyroid Neoplasms
Pancreas
Condensation
Lung Neoplasms
Prostatic Neoplasms
Colon
Leukemia
Breast
Neoplasms

ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Molecular Medicine
  • Organic Chemistry
  • Analytical Chemistry
  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

Cite this

Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs. / Pettit, George; Rosenberg, Heidi J.; Dixon, Rachel; Knight, John C.; Hamel, Ernest; Chapuis, Jean; Pettit, Robin; Hogan, Fiona; Sumner, Brandy; Ain, Kenneth B.; Trickey-Platt, Brindi.

In: Journal of Natural Products, Vol. 75, No. 3, 23.03.2012, p. 385-393.

Research output: Contribution to journalArticle

Pettit, G, Rosenberg, HJ, Dixon, R, Knight, JC, Hamel, E, Chapuis, J, Pettit, R, Hogan, F, Sumner, B, Ain, KB & Trickey-Platt, B 2012, 'Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs', Journal of Natural Products, vol. 75, no. 3, pp. 385-393. https://doi.org/10.1021/np200797x
Pettit, George ; Rosenberg, Heidi J. ; Dixon, Rachel ; Knight, John C. ; Hamel, Ernest ; Chapuis, Jean ; Pettit, Robin ; Hogan, Fiona ; Sumner, Brandy ; Ain, Kenneth B. ; Trickey-Platt, Brindi. / Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs. In: Journal of Natural Products. 2012 ; Vol. 75, No. 3. pp. 385-393.
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