Antimitotic activity of diaryl compounds with structural features resembling combretastatin A-4.
Series of diaryl ethers, amines and amides have been synthesized and tested for antitumor activity. These diaryl compounds possess some of the structural features of combretastatin A-4 (a potent antimitotic agent). They were designed to discover whether transferring these structural motifs from stilbenes to heterosubstituted diaryl compounds would enhance their biochemical activities. Molecular modeling studies suggested that these diaryl compounds could adopt conformations similar to combretastatin A-4. However, although some agents (5-7) were cytotoxic and others (10 and 12) could interact with tubulin, none were as potent as combretastatin A-4.
Aleksandrzak
K
K
Cancer Research Campaign Section of Drug Development and Imaging, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
McGown
A T
AT
Hadfield
J A
JA
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001632:Bibenzyls / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D007941:Leukemia P388 / Q000188:drug therapy*; D051379:Mice; D013267:Stilbenes; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D013267:Stilbenes; C040105:combretastatin