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.

Parrino, B., Carbone, A., Spanò, V., Montalbano, A., Giallombardo, D., Barraja, P., et al. (2015). Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 94, 367-377 [10.1016/j.ejmech.2015.03.009].

Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity

PARRINO, Barbara;CARBONE, Anna;SPANO', Virginia;MONTALBANO, Alessandra;GIALLOMBARDO, Daniele;BARRAJA, Paola;ATTANZIO, Alessandro;TESORIERE, Luisa;CIRRINCIONE, Girolamo;DIANA, Patrizia
2015

Abstract

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.
Settore CHIM/08 - Chimica Farmaceutica
Settore ING-IND/22 - Scienza E Tecnologia Dei Materiali
http://www.journals.elsevier.com/european-journal-of-medicinal-chemistry/
Parrino, B., Carbone, A., Spanò, V., Montalbano, A., Giallombardo, D., Barraja, P., et al. (2015). Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 94, 367-377 [10.1016/j.ejmech.2015.03.009].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/147542
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