Unsaturated genistein disaccharide glycoside as a novel agent affecting microtubules.
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.
Rusin
Aleksandra
A
Department of Tumor Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Branch Gliwice, Wybrzeze AK 15, Gliwice, Poland.
Gogler
Agnieszka
A
Głowala-Kosińska
Magdalena
M
Bochenek
Daria
D
Gruca
Aleksandra
A
Grynkiewicz
Grzegorz
G
Zawisza
Jadwiga
J
Szeja
Wiesław
W
Krawczyk
Zdzisław
Z
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D019833:Genistein / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
C544968:7-O-(2,3,4,6-tetra-O-acetylgalactopyranosyl)-1-4-(6-O-acetylhex-2-enepyranosyl)genistein; D000970:Antineoplastic Agents; D004187:Disaccharides; D006027:Glycosides; D050257:Tubulin Modulators; D019833:Genistein