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.
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 [10.1021/jm070834t].
ISOINDOLO[2,1-a]QUINOXALINE DERIVATIVES, NOVEL POTENT ANTITUMOR AGENTS WITH DUAL INHIBITION OF TUBULIN POLYMERIZATION AND TOPOISOMERASE I
DIANA, Patrizia;MARTORANA, Annamaria;BARRAJA, Paola;MONTALBANO, Alessandra;DATTOLO, Gaetano;CIRRINCIONE, Girolamo;
2008-01-01
Abstract
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.File | Dimensione | Formato | |
---|---|---|---|
jm070834t.pdf
Solo gestori archvio
Descrizione: pdf
Dimensione
1.13 MB
Formato
Adobe PDF
|
1.13 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.