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ID: ALA2021895

Journal: Eur J Med Chem

Title: Conformationnally restricted naphthalene derivatives type isocombretastatin A-4 and isoerianin analogues: synthesis, cytotoxicity and antitubulin activity.

Authors: Rasolofonjatovo E, Provot O, Hamze A, Rodrigo J, Bignon J, Wdzieczak-Bakala J, Desravines D, Dubois J, Brion JD, Alami M.

Abstract: A novel series of dihydronaphtalene, tetrahydronaphtalene and naphtalene derivatives as restricted analogues of isoCA-4 were designed, synthesized and evaluated for their anticancer properties. High cell growth inhibition against four tumour cell lines was observed at a nanomolar level with dihydronaphtalenes 1d, e and 1h, tetrahydronaphtalene 2c and naphtalene 3c. Structure-activity relationships are also considered. These compounds exhibited a significant inhibitory activity toward tubulin polymerization (IC(50) = 2-3 μM), comparable to that of isoCA-4. The effect of the lead compounds 1e and 2c on the cancer cells tested was associated with cell cycle arrest in the G(2)/M phase. Docking studies reveal that these compounds showed a binding mode similar to those observed with their non-constraint isoCA-4 and isoerianin congeners.

CiteXplore: 22449653

DOI: 10.1016/j.ejmech.2012.03.001