Design, synthesis, biochemical, and biological evaluation of nitrogen-containing trifluoro structural modifications of combretastatin A-4.
A new trifluorinated amino-combretastatin analogue, (Z)-2-(4'-methoxy-3'-aminophenyl)-1-(3,4,5-trifluorophenyl)ethene, prepared by chemical synthesis, was found to be a potent inhibitor of tubulin assembly (IC(50)=2.9 microM), and cytotoxic against selected human cancer cell lines. This new lead compound is among the most active from a group of related structural modifications.
Hall
John J
JJ
Department of Chemistry and Biochemistry, Baylor University, One Bear Place #97348, Waco, TX 76798-7348, USA.
Sriram
Madhavi
M
Strecker
Tracy E
TE
Tidmore
Justin K
JK
Jelinek
Christopher J
CJ
Kumar
G D Kishore
GD
Hadimani
Mallinath B
MB
Pettit
George R
GR
Chaplin
David J
DJ
Trawick
Mary Lynn
ML
Pinney
Kevin G
KG
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001632:Bibenzyls / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology*
C532011:(Z)-2-(4'-methoxy-3'-aminophenyl)-1-(3,4,5-trifluorophenyl)ethene; D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D006845:Hydrocarbons, Fluorinated; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C058728:fosbretabulin