Synthesis of the Macrolactone of Migrastatin and Analogues with Potent Cell-Migration Inhibitory Activity

The synthesis of the macrolactone core of migrastatin 2, its potent anti-metastasis analogue 34, and ester derivatives 35 and 38 are reported. The approach involves the use of a dihydroxylation reaction to establish the desired C-8 stereocenter followed by a metathesis cyclization reaction. The effects of the compounds on the migration and invasion of human breast cancer cells were evaluated by using the wound-healing and the Boyden-chamber cell-migration and cell-invasion assays. The results revealed a high potency of the macrolactones 2 and 34 and the ester analogues 35 and 38, which suggests they have potential as antimetastatic agents.

Fundo de Apoio ao Ensino e Pesquisa da UNICAMP (FAEP-UNICAMP)

Fundo de Apoio ao Ensino e Pesquisa - UNICAMP

Fundacao de Apoio ao Ensino e Pesquisa do Estado de Sao Paulo (FAPESP)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Instituto Nacional de Ciencia e Tecnologia de Farmacos e Medicamentos (INCT-INOFAR)[Proc. CNPq573.564/2008-6]

Instituto Nacional de Ciencia e Tecnologia de Farmacos e Medicamentos (INCT-INOFAR)