RESUMO
Genistein, due to its recognized chemopreventive and antitumor potential, is a molecule of interest as a lead compound in drug design. While multiple molecular targets for genistein have been identified, so far neither for this isoflavonoid nor for its natural or synthetic derivatives disruption of microtubules and mitotic spindles has been reported. Here we describe such properties of the synthetic glycosidic derivative of genistein significantly more cytotoxic than genistein, 7-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-(6-O-acetyl-hex-2-ene-alpha-D-erythro-pyranosyl)genistein, shortly named G21. We found that G21 causes significant mitotic delay, frequent appearance of multipolar spindles, and alteration of the interphase microtubule array.
Assuntos
Antineoplásicos/química , Dissacarídeos/química , Genisteína/análogos & derivados , Glicosídeos/química , Microtúbulos/efeitos dos fármacos , Moduladores de Tubulina/química , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Dissacarídeos/síntese química , Dissacarídeos/toxicidade , Genisteína/síntese química , Genisteína/química , Genisteína/toxicidade , Glicosídeos/síntese química , Glicosídeos/toxicidade , Humanos , Microtúbulos/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/toxicidadeRESUMO
The ability of newly synthesized genistein benzyl and glycosylated derivatives to permeabilize the liposome membrane was studied by calcein-leakage method. All studied derivatives appeared to be more effective than their parent compound--genistein. Comparing the experimental results with theoretical calculations we found that in the case of benzyl derivatives the dipole moment of added benzene ring (with its substitutions) might be important for the strength of flavonoids-lipid interactions. This conclusion may have some implications for QSAR studies in which mostly the dipole moments of entire molecules are considered.
