Novel sulfonate analogues of combretastatin A-4: potent antimitotic agents.
Sulfonate analogues of combretastatin A-4 have been prepared. These compounds compete with colchicine and combretastatin A-4 for the colchicine binding site on tubulin and are potent inhibitors of tubulin polymerization and cell proliferation. Importantly, these compounds also inhibit the proliferation of P-glycoprotein positive (+) cancer cells, which are resistant to many other antitumor agents.
Gwaltney
S L
SL
Cancer Research, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. stephen.gwaltney@abbott.com
Imade
H M
HM
Barr
K J
KJ
Li
Q
Q
Gehrke
L
L
Credo
R B
RB
Warner
R B
RB
Lee
J Y
JY
Kovar
P
P
Wang
J
J
Nukkala
M A
MA
Zielinski
N A
NA
Frost
D
D
Ng
S C
SC
Sham
H L
HL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D003078:Colchicine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D011108:Polymers / Q000378:metabolism; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D011108:Polymers; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C058728:fosbretabulin; D003078:Colchicine