Synthesis and biological evaluation of novel anticancer bivalent colchicine–tubulizine hybrids

International audienc

Synthesis of Chlorin-(Arylamino)quinazoline Hybrids as Models for Multifunctional Drug Development

A series of multifunctional conjugates each consisting of a fluorescent chlorin photosensitizer and an (arylamino)quinazoline-based epidermal growth factor receptor/vascular endothelial growth factor receptor ligand, potentially useful in site-selective photodynamic antitumor therapy, were prepared and their photochemical properties were investigated

Discovery of dihydrofuranoallocolchicinoids - Highly potent antimitotic agents with low acute toxicity

International audienceTwo series of heterocyclic colchicinoids bearing β-methylenedihydrofuran or 2H-pyran-2-one fragments were synthesized by the intramolecular Heck reaction. Methylenedihydrofuran compounds 9a and 9h were found to be the most cytotoxic among currently known colchicinoids, exhibiting outstanding antiproliferative activity on tumor cell lines in picomolar (0.01-2.1 nM) range of concentrations. Compound 9a potently and substoichiometrically inhibits microtubule formation in vitro, being an order of magnitude more active in this assay than colchicine. Derivatives 9a and 9h revealed relatively low acute toxicity in mice (LD50 ≥ 10 mg/kg i.v.). The X-Ray structure of colchicinoid 9a bound to tubulin confirmed interaction of this compound with the colchicine binding site of tubulin