A new series of pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines, was conveniently prepared using a versatile and high yielding multistep sequence. A good number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against three different human tumor cell lines with EC50 (0.08–4.96 μM) values reaching the nanomolar level. Selected compounds were investigated by laser flash photolysis. The most photocytotoxic derivative, exhibiting a fairly long-lived triplet state (τ ∼ 7 μs) and absorbance in the UV–Vis, was tested in the photo-oxidations of 9,10-anthracenedipropionic acid (ADPA) by singlet oxygen. The photosentizing properties are responsible for the compounds’ ability to photoinduce massive cell death with involvement of mitochondria.

Spanò, V., Frasson, I., Giallombardo, D., Doria, F., Parrino, B., Carbone, A., et al. (2016). Synthesis and antiproliferative mechanism of action of pyrrolo[3′,2′:6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 123, 447-461 [10.1016/j.ejmech.2016.07.051].

Synthesis and antiproliferative mechanism of action of pyrrolo[3′,2′:6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers

SPANO', Virginia;GIALLOMBARDO, Daniele;PARRINO, Barbara;CARBONE, Anna;MONTALBANO, Alessandra;DIANA, Patrizia;CIRRINCIONE, Girolamo;BARRAJA, Paola
2016-10-10

Abstract

A new series of pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines, was conveniently prepared using a versatile and high yielding multistep sequence. A good number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against three different human tumor cell lines with EC50 (0.08–4.96 μM) values reaching the nanomolar level. Selected compounds were investigated by laser flash photolysis. The most photocytotoxic derivative, exhibiting a fairly long-lived triplet state (τ ∼ 7 μs) and absorbance in the UV–Vis, was tested in the photo-oxidations of 9,10-anthracenedipropionic acid (ADPA) by singlet oxygen. The photosentizing properties are responsible for the compounds’ ability to photoinduce massive cell death with involvement of mitochondria.
Settore CHIM/08 - Chimica Farmaceutica
Settore ING-IND/22 - Scienza E Tecnologia Dei Materiali
https://www.sciencedirect.com/science/article/pii/S0223523416306146?via=ihub
Spanò, V., Frasson, I., Giallombardo, D., Doria, F., Parrino, B., Carbone, A., et al. (2016). Synthesis and antiproliferative mechanism of action of pyrrolo[3′,2′:6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 123, 447-461 [10.1016/j.ejmech.2016.07.051].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/190036
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