Synthesis and biological activities of (R)- and (S)- N -(4-Methoxyphenyl)- N,2,6-trimethyl-6,7-dihydro-5 H -cyclopenta[ d ]pyrimidin-4-aminium chloride as potent cytotoxic antitubulin agents

Aleem Gangjee, Ying Zhao, Ernest Hamel, Cara Westbrook, Susan L. Mooberry

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

(R,S)-1 is a potent antimitotic compound. (R)-1·HCl and (S)-1·HCl were synthesized from (R)- and (S)-3-methyladipic acid. Both enantiomers were potent inhibitors of cell proliferation and caused cellular microtubule loss and mitotic arrest. They inhibited purified tubulin assembly and the binding of [3H]colchicine to tubulin, with (S)-1 being about twice as potent. Cytotoxicity against 60 tumor cell lines, however, indicated that the (S)-isomer was 10- to 88-fold more potent than the (R)-isomer.

Original languageEnglish (US)
Pages (from-to)6151-6155
Number of pages5
JournalJournal of Medicinal Chemistry
Volume54
Issue number17
DOIs
StatePublished - Sep 8 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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