Synthesis and evaluation of Apogossypol atropisomers as potential Bcl-xL antagonists.
Anti-apoptotic Bcl-2 family proteins such as Bcl-2 and Bcl-X(L) have been recently validated as targets for the discovery of novel anti-cancer agents. We previously reported that racemic (+/-) Apogossypol, a semi-synthetic compound derived from the natural product Gossypol, binds and inhibits Bcl-2 and Bcl-X(L)in vitro and in cell. Given that (+) and (-) Gossypol display different proapoptotic activities, here we report on the synthesis of (+) and (-) Apogossypol and the evaluation of their in vitro and cellular activity.
Wei
Jun
J
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Rega
Michele F
MF
Kitada
Shinichi
S
Yuan
Hongbin
H
Zhai
Dayong
D
Risbood
Prabhakar
P
Seltzman
Herbert H
HH
Twine
Charles E
CE
Reed
John C
JC
Pellecchia
Maurizio
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005454:Fluorescence Polarization; D006072:Gossypol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D051020:bcl-X Protein / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; C492806:apogossypol; D051020:bcl-X Protein; D006072:Gossypol
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