Antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'-trimethoxyphenyl)-2-nitro-ethylene.
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 < or = 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 time-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 (GI50=1-4 microg ml(-1)), and weakly inhibited mammalian tubulin polymerization (IC50=0.60 microg ml(-1)).
Pettit
R K
RK
Cancer Research Institute and Department of Microbiology, Arizona State University, Tempe, 85287-2404, USA. pettitr@asu.edu
Hamel
E
E
Verdier-Pinard
P
P
Roberson
R W
RW
Hazen
K C
KC
Pettit
G R
GR
Crews
Laura C
LC
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D001555:Benzene Derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D001704:Biopolymers / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005030:Ethylenes / Q000494:pharmacology* / Q000627:therapeutic use; D005658:Fungi / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008826:Microbial Sensitivity Tests; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
C462659:1-(3',4',5'-trimethoxyphenyl)-2-nitroethylene; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D001704:Biopolymers; D005030:Ethylenes; D014404:Tubulin