TY - JOUR
T1 - Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity
AU - Diana, Patrizia
AU - Tesoriere, Luisa
AU - Carbone, Anna
AU - Spano', Virginia
AU - Giallombardo, Daniele
AU - Cirrincione, Girolamo
AU - Montalbano, Alessandra
AU - Parrino, Barbara
AU - Barraja, Paola
AU - Attanzio, Alessandro
AU - Sissi, Claudia
AU - Palumbo, Manlio
PY - 2015
Y1 - 2015
N2 - Three new ring systems, pyrido[2′,3′:3,4]pyrrolo[1,2-a]quinoxalines, pyrido[3′,2′:3,4]pyrrolo[1,2-a]quinoxalines and pyrido[2′,3′:5,6]pyrazino[2,1-a]isoindoles, were synthesized through an aza-substitution on the already active isoindolo-quinoxaline system and in particular in the position 7 or 4 of the isoindole moiety and in position 5 of the quinoxaline portion. All new compounds were screened by the National Cancer Institute (Bethesda, MD) against a panel of 60 human tumor cell lines. Biological results of the most active derivatives, with pGI50 values between 7.09 and 7.27, confirmed the importance of the presence of methoxy substituents for biological activity. The anti-proliferative effect of selected quinoxalines was associated with apoptosis of the cells and arrest in G2/M phase of the cell cycle. DNA binding properties of the compounds was also assessed to investigate the possible mechanism of action.
AB - Three new ring systems, pyrido[2′,3′:3,4]pyrrolo[1,2-a]quinoxalines, pyrido[3′,2′:3,4]pyrrolo[1,2-a]quinoxalines and pyrido[2′,3′:5,6]pyrazino[2,1-a]isoindoles, were synthesized through an aza-substitution on the already active isoindolo-quinoxaline system and in particular in the position 7 or 4 of the isoindole moiety and in position 5 of the quinoxaline portion. All new compounds were screened by the National Cancer Institute (Bethesda, MD) against a panel of 60 human tumor cell lines. Biological results of the most active derivatives, with pGI50 values between 7.09 and 7.27, confirmed the importance of the presence of methoxy substituents for biological activity. The anti-proliferative effect of selected quinoxalines was associated with apoptosis of the cells and arrest in G2/M phase of the cell cycle. DNA binding properties of the compounds was also assessed to investigate the possible mechanism of action.
UR - http://hdl.handle.net/10447/147542
UR - http://www.journals.elsevier.com/european-journal-of-medicinal-chemistry/
M3 - Article
VL - 94
SP - 367
EP - 377
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -