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

Girolamo Cirrincione, Paola Barraja, Patrizia Diana, Alessandra Montalbano, Virginia Spano', Barbara Parrino, Anna Carbone, Daniele Giallombardo, Mauro Freccero, Sara N. Richter, Filippo Doria, Matteo Nadai, Ilaria Frasson

Risultato della ricerca: Article

10 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)447-461
Numero di pagine15
RivistaEuropean Journal of Medicinal Chemistry
Volume123
Stato di pubblicazionePublished - 2016

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Singlet Oxygen
Photosensitizing Agents
Photolysis
Tumor Cell Line
Amines
Mitochondria
Lasers
Cell Death
Derivatives
Acids
Photooxidation
Cell death
Tumors
Cells
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Organic Chemistry
  • Drug Discovery

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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",
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.",
keywords = "Antiproliferative activity; Photodynamic therapy; Photosensitizing agents; Pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines; Reactive oxygen species; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; Pharmacology",
author = "Girolamo Cirrincione and Paola Barraja and Patrizia Diana and Alessandra Montalbano and Virginia Spano' and Barbara Parrino and Anna Carbone and Daniele Giallombardo and Mauro Freccero and Richter, {Sara N.} and Filippo Doria and Matteo Nadai and Ilaria Frasson",
year = "2016",
language = "English",
volume = "123",
pages = "447--461",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

TY - JOUR

T1 - Synthesis and antiproliferative mechanism of action of pyrrolo[3′,2′:6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers

AU - Cirrincione, Girolamo

AU - Barraja, Paola

AU - Diana, Patrizia

AU - Montalbano, Alessandra

AU - Spano', Virginia

AU - Parrino, Barbara

AU - Carbone, Anna

AU - Giallombardo, Daniele

AU - Freccero, Mauro

AU - Richter, Sara N.

AU - Doria, Filippo

AU - Nadai, Matteo

AU - Frasson, Ilaria

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Antiproliferative activity; Photodynamic therapy; Photosensitizing agents; Pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines; Reactive oxygen species; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; Pharmacology

UR - http://hdl.handle.net/10447/190036

UR - http://www.journals.elsevier.com/european-journal-of-medicinal-chemistry/

M3 - Article

VL - 123

SP - 447

EP - 461

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -