Organic & Biomolecular Chemistry 2005-06-07

Synthesis and biological evaluation of novel fumagillin and ovalicin analogues.

Ralph Mazitschek, Axel Huwe, Athanassios Giannis

Index: Org. Biomol. Chem. 3(11) , 2150-4, (2005)

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Abstract

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.