Design, synthesis, and biological testing of pyrazoline derivatives of combretastatin-A4

Marlie Johnson, Brent Younglove, Lauren Lee, Regan LeBlanc, Herman Holt, Patrice Hills, Hilary Mackay, Toni Brown, Susan L. Mooberry, Moses Lee

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


Fourteen N-acetylated and non-acetylated 3,4,5-tri- or 2,5-dimethoxypyrazoline analogs of combretastatin-A4 (1) were synthesized. A non-acetylated derivative (5a) with the same substituents as CA-4 (1) was the most active compound in the series, with IC50 values of 2.1 and 0.5 μM in B16 and L1210 cell lines, respectively. In contrast, a similar compound with an acetyl group at N1 of the pyrazoline ring (6g) showed poor activity in the cell lines studied. A cell-based assay indicated that compound 5a caused extensive microtubule depolymerization with an EC50 value of 7.1 μM in A-10 cells while no activity was seen with the acetylated compound. Molecular modeling studies showed that these compounds possess a twisted conformation similar to CA-4 (1).

Original languageEnglish (US)
Pages (from-to)5897-5901
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number21
StatePublished - Nov 1 2007


  • Achiral
  • Anti-cancer
  • CC-1065
  • Combretastatins
  • Dimer
  • Duocarmycins
  • Pyrazolines
  • Pyrrolobenzodiazepines
  • Tubulin
  • seco-Amino-CBI

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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