Synthesis and biological evaluation of novel fumagillin and ovalicin analogues.
A promising approach among the numerous efforts to cure cancer is the interruption of the tumour-induced formation of new blood vessels (angiogenesis). By suppressing angiogenesis with drugs, the tumour can neither grow to a life threatening size, nor metastasize. The natural product fumagillin 1 and the structurally related ovalicin 2 are two of the most potent anti-angiogenic compounds. Here, we report the design and synthesis of novel fumagillin and ovalicin analogues lacking reactive epoxy functionalities, which were thought to be responsible for the severe toxic side-effects observed. We also report a new synthetic approach and the determination of the anti-angiogenic properties of these compounds in endothelial cells.
Mazitschek
Ralph
R
The Broad Institute, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02141, USA. ralph_mazitschek@hms.harvard.edu
Huwe
Axel
A
Giannis
Athanassios
A
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C002781:ovalicin; C026211:fumagillin