Phenylcinnamides as novel antimitotic agents

Benjamin J. Leslie, Clinton R. Holaday, Tran Nguyen, Paul J. Hergenrother

Research output: Contribution to journalArticlepeer-review

Abstract

Compound 8H is a phenylcinnamide that induces G2/M-phase cell cycle arrest and cell death in cancer cell lines. Here we show that 8H exerts its cytotoxic activity through disruption of microtubule dynamics in vitro and in cell culture. A series of cinnamide derivatives were synthesized and evaluated, and several new compounds were identified that improve on the activity of the parent compound, with IC50 values for induction of cell death ranging from 1 to 10 μM. Notably, these compounds retain potency in the HL-60/VCR leukemia cell line, which is resistant to antimitotic cancer drugs vincrisitine and paclitaxel through up-regulation of P-glycoprotein drug efflux pumps. As P-glycoprotein expression is often responsible for drug resistance in cancer and the exclusion of compounds from the central nervous system, 8H and its derivatives merit further examination as potential antimitotic therapeutics, specifically for brain cancers and cancers that are resistant to standard antimitotic agents.

Original languageEnglish (US)
Pages (from-to)3964-3972
Number of pages9
JournalJournal of Medicinal Chemistry
Volume53
Issue number10
DOIs
StatePublished - May 27 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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