Antifungal phenylethylene

• US 20050014849A1
• Filed: 12/20/2002
• Published: 01/20/2005
• Est. Priority Date: 12/22/2001
• Status: Abandoned Application

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Pettit, George R., Pettit, Robin K.
• Application Number:
  US10/499,958
• Publication Number:
  US 20050014849A1
• Time in Patent Office: Days
• US Class Current: 514/716
• CPC Class Codes: A61K 31/09 having two or more such linkages
• CPC Class Codes: C07C 205/32 having nitro groups bound to acyclic carbon atoms and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton

Abstract

The antifungal and cancer cell growth inhibitory activities of 1-(3′,4′,5′-trimethoxyphenyl)-2-nitro-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 ≦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. TMPN was slightly cytotoxic for murine and human cancer cell lines (GI₅₀=1-4 μg/ml), and weakly inhibited mammalian tubulin polymerization (IC₅₀=0.60 μg/ml). TMPN may also be used as a biochemical probe for tubulin and fungal dimorphism studies.

Claims

1. A method of treating a host afflicted by a fungi (this includes yeast and filamentous forms) by administering an effective amount of 1-(3′

,4,′

5′

-trimethoxyphenyl)-2-nitro-ethylene thereto.

2. The method according to claim 1 wherein said administration is systemic.

3. The method according to claim 1 wherein said administration is topical.

4. A method of using an effective amount of 1-(3′

,4,′

5′

-trimethoxyphenyl)-2-nitro-ethylene as a biochemical probe.

5. A method according to claim 4 wherein said probe is used to investigate fungal dimorphism.