Synthesis and biological evaluation of phorboxazole congeners leading to the discovery and preparative-scale synthesis of (+)-chlorophorboxazole A possessing picomolar human solid tumor cell growth inhibitory activity

Amos B. Smith, Thomas M. Razler, Regina M. Meis, George Pettit

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

(Chemical Equation Presented) Highly convergent syntheses of eight phorboxazole congeners and their evaluation against a diverse panel of human solid tumor cancer cell lines have been achieved. Specifically, the C(45-46) alkyne, alkene, and alkane phorboxazole A analogues [(+)-4-(+)-6] were constructed and found to display single digit nanomolar cell growth inhibitory activities in a series of human cancer cell lines. The structurally simplified C(11-15)-acetal congener (+)-20Z also proved potent albeit reduced (cf. 34.6 nM) when evaluated against the same cell line panel. Importantly, (+)-C(46)-chlorophorboxazole A (3) displayed picomolar (pM) inhibitory activity in several cell lines.

Original languageEnglish (US)
Pages (from-to)1201-1208
Number of pages8
JournalJournal of Organic Chemistry
Volume73
Issue number4
DOIs
StatePublished - Feb 15 2008

ASJC Scopus subject areas

  • Organic Chemistry

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