1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4

Lauren Lee, Ryan Davis, Jenna Vanderham, Patrice Hills, Hilary Mackay, Toni Brown, Susan L. Mooberry, Moses Lee

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity (IC50 < 1 μM for L1210 and <10 μM for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 μM, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity.

Original languageEnglish (US)
Pages (from-to)2011-2015
Number of pages5
JournalEuropean Journal of Medicinal Chemistry
Volume43
Issue number9
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

    Fingerprint

Keywords

  • Chalcone
  • Combretastatin
  • Cytotoxicity
  • Thiourea
  • Tubulin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this