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Antifungal and cancer cell growth inhibitory activities of 1-(3 ',4 ',5 '-trimethoxyphenyl)-2-vitro-ethylene

  1. Author:
    Pettit, R. K.
    Hamel, E.
    Verdier-Pinard, P.
    Roberson, R. W.
    Hazen, K. C.
    Pettit, G. R.
    Crews, L. C.

  2. Author Address

    Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA Arizona State Univ, Dept Mol & Cellular Biol, Tempe, AZ 85287 USA Arizona State Univ, Dept Plant Biol & Chem, Tempe, AZ 85287 USA NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diagnosis, Screening Technol Branch,Dev Therapeut Program, Frederick, MD USA Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA Pettit RK Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA
    1. Year: 2002
  2. Journal: Mycoses
    1. 45
    2. 3-4
    3. Pages: 65-74
  4. Type of Article: Article
  1. Abstract:

    The antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'-trimethoxyphenyl)-2-vitro-ethylene (TMPN) were examined. TMPN was fungicidal for the majority of 132 reference strains and clinical isolates tested, including those resistant to fluconazole, ketoconazole, amphotericin B or flucytosine. Minimum fungicidal concentration/minimum inhibitory concentration (MFC/MIC) ratios were less than or equal to 2 for 96% of Cryptococcus neoformans clinical isolates and 71% of Candida albicans clinical isolates. TMPN was fungicidal for a variety of other basidiomycetes, endomycetes and hyphomycetes, and its activity was unaffected by alterations in media pH. The frequency of occurrence of fungal spontaneous mutations to resistance was < 10(-6). Kill-curve analyses confirmed the fungicidal action of TMPN, and demonstrated that killing was concentration- and tithe-dependent. At sub-MIC exposure to TMPN, C. albicans did not exhibit yeast/hyphae switching. TMPN was slightly cytotoxic for murine and human cancer cell lines (GI(50) = 1-4 mug ml(-1)), and weakly inhibited mammalian tubulin polymerization (IC50 = 0.60 mug ml(-1)).

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