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Title: Synthesis and antiproliferative mechanism of action of pyrrolo[3',2':6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers. Author: Spanò V, Frasson I, Giallombardo D, Doria F, Parrino B, Carbone A, Montalbano A, Nadai M, Diana P, Cirrincione G, Freccero M, Richter SN, Barraja P. Journal: Eur J Med Chem; 2016 Nov 10; 123():447-461. PubMed ID: 27490024. 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.[Abstract] [Full Text] [Related] [New Search]