title: Synthesis and antiproliferative mechanism of action of pyrrolo[3',2':6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers.
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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Spanò
authors.affiliation: Dipartimento di Medicina Molecolare, Università degli Studi di Padova, Via Gabelli 63, 35121 Padova, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Frasson
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Giallombardo
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Pavia, Viale Taramelli 10, 27100 Pavia, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Doria
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Parrino
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Carbone
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Montalbano
authors.affiliation: Dipartimento di Medicina Molecolare, Università degli Studi di Padova, Via Gabelli 63, 35121 Padova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Nadai
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Diana
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Cirrincione
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Pavia, Viale Taramelli 10, 27100 Pavia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Freccero
authors.affiliation: Dipartimento di Medicina Molecolare, Università degli Studi di Padova, Via Gabelli 63, 35121 Padova, Italy.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Richter
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy. Electronic address: paola.barraja@unipa.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Barraja
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D010782:Photolysis / Q000187:drug effects / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D026082:Singlet Oxygen / Q000378:metabolism*
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D026082:Singlet Oxygen
keywords: Antiproliferative activity; Photodynamic therapy; Photosensitizing agents; Pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines; Reactive oxygen species