Antineoplastic agents 440. Asymmetric synthesis and evaluation of the combretastatin A-1 SAR probes (1S,2S)- and (1R,2R)-1,2-dihydroxy-1-(2',3'-dihydroxy-4'-methoxyphenyl)-2-(3'' ,4'',5''-trimethoxyphenyl)-ethane

George R. Pettit, John W. Lippert, Delbert L. Herald, Ernest Hamel, Robin K. Pettit

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The synthetic (E)-isomer (3b) of natural combretastatin A-1 (1a) isolated from the African bushwillow Combretum caffrum was the focus of chiral hydroxylation (Sharpless) reactions as part of a structure-activity relationship study. The resulting (R,R)- and (S,S,)-diols (6 and 7) and synthetic intermediates were evaluated against a series of cancer cell lines, microorganisms, and tubulin. Chiral diols 6 and 7 showed increased activity against the P-388 murine lymphocytic leukemia cell line with ED50 values of 3.9 and 2.9 μg/mL, respectively, when compared to the precursor (E)-stilbene 3b. In contrast, (E)-stilbene 3b exhibited more potent antibiotic activity than the chiral diols (6 and 7). Both diols, (R,R)-6 and (S,S)-7, displayed less cancer cell growth inhibition and less antibiotic activity than did natural combretastatin A-1 (1a) (P-388 ED50 0.25 μg/mL).

Original languageEnglish (US)
Pages (from-to)969-974
Number of pages6
JournalJournal of Natural Products
Volume63
Issue number7
DOIs
StatePublished - 2000

ASJC Scopus subject areas

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

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