E-Combretastatin and E-resveratrol structural modifications: antimicrobial and cancer cell growth inhibitory beta-E-nitrostyrenes.
As part of a broad-based SAR investigation of E-resveratrol (strong sirtuin activator and antineoplastic) and the anticancer vascular-targeting combretastatin-type stilbenes, a series of twenty-three beta-E-nitrostyrenes was synthesized in order to evaluate potential antineoplastic, antitubulin, and antimicrobial activities. The beta-E-nitrostyrenes evaluated ranged from monosubstituted phenols to trimethoxy and 3-methoxy-4,5-methylenedioxy derivatives. Two of the beta-nitrostyrenes were synthesized as water-soluble sodium phosphate derivatives (4t, 4v). All except four (4r, 4s, 4t, 4u) of the series significantly inhibited a minipanel of human cancer cell lines. All but eight led to an IC(50) of <10 microM for inhibition of tubulin polymerization, and all except three (4l, 4t, 4v) displayed antimicrobial activity.
Pettit
Robin K
RK
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, PO Box 871604, Tempe, AZ 85287-1604, United States. robin.pettit@asu.edu
Pettit
George R
GR
Hamel
Ernest
E
Hogan
Fiona
F
Moser
Bryan R
BR
Wolf
Sonja
S
Pon
Sandy
S
Chapuis
Jean-Charles
JC
Schmidt
Jean M
JM
D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001632:Bibenzyls / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D001632:Bibenzyls; D013267:Stilbenes; D013343:Styrenes; D014404:Tubulin; D050257:Tubulin Modulators; C011955:beta-nitrostyrene; C040105:combretastatin; D000077185:Resveratrol