Isoindoloquinoxalines 4 and 5 were obtained by refluxing 2-(2′-aminoaryl)-1-cyanoisoindoles 3a-e in acetic or formic acid. All derivatives were screened by the National Cancer Institute (Bethesda, MD) for the in vitro one dose primary anticancer assay against a 3-cell line panel. Compounds 4a-e, screened against a panel of about 60 human tumor cell lines, showed remarkable antineoplastic activity; they had GI50 values in the low micromolar or submicromolar range and reached, in the case of 4c, nanomolar concentrations on 88% of the 59 tested cell lines. Flow cytometric analysis of cell cycle after treatment with 4c demonstrated an arrest of the cell cycle in G2/M phase. This effect was accompanied with apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, and activation of caspase-3 and caspase- 9. Moreover, 4c induced a clear increase in the mitotic index, inhibited microtubule assembly in vitro, and interestingly also acted as a topoisomerase I inhibitor.
|Data di pubblicazione:||2008|
|Titolo:||ISOINDOLO[2,1-a]QUINOXALINE DERIVATIVES, NOVEL POTENT ANTITUMOR AGENTS WITH DUAL INHIBITION OF TUBULIN POLYMERIZATION AND TOPOISOMERASE I|
|Autori:||DIANA P; MARTORANA A; BARRAJA P; MONTALBANO A; DATTOLO G; CIRRINCIONE G; DALL'ACQUA F; SALVADOR A; VEDALDI D; BASSO G; VIOLA G|
|Tipologia:||Articolo su rivista|
|Citazione:||DIANA P, MARTORANA A, BARRAJA P, MONTALBANO A, DATTOLO G, CIRRINCIONE G, et al. (2008). ISOINDOLO[2,1-a]QUINOXALINE DERIVATIVES, NOVEL POTENT ANTITUMOR AGENTS WITH DUAL INHIBITION OF TUBULIN POLYMERIZATION AND TOPOISOMERASE I. JOURNAL OF MEDICINAL CHEMISTRY, 51, 2387-2399.|
|Digital Object Identifier (DOI):||10.1021/jm070834t|
|Appare nelle tipologie:||01 - Articolo su rivista|