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New tricyclic systems as photosensitizers towards triple negative breast cancer cells

Nineteen pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones were synthesized as new tricyclic systems in which the pyridine ring is annelated to the 6,7-dihydroindolizin-8(5H)-one and 5,6,7,8-tetrahydro-9H-pyrrole[1,2-a]azepine-9-one moieties to obtain potential photosensi...

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Detalles Bibliográficos
Autores principales: Barreca, Marilia, Ingarra, Angela Maria, Raimondi, Maria Valeria, Spanò, Virginia, Piccionello, Antonio Palumbo, De Franco, Michele, Menilli, Luca, Gandin, Valentina, Miolo, Giorgia, Barraja, Paola, Montalbano, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pharmaceutical Society of Korea 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701179/
https://www.ncbi.nlm.nih.gov/pubmed/36399284
http://dx.doi.org/10.1007/s12272-022-01414-1
Descripción
Sumario:Nineteen pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones were synthesized as new tricyclic systems in which the pyridine ring is annelated to the 6,7-dihydroindolizin-8(5H)-one and 5,6,7,8-tetrahydro-9H-pyrrole[1,2-a]azepine-9-one moieties to obtain potential photosensitizing agents. They were tested for their photoantiproliferative activity on a triple-negative breast cancer cell line, MDA-MB-231, in the dark and under UVA light (2.0 J/cm(2)). We demonstrated that their toxicity, only when exposed to light, was primarily due to the generation of reactive oxygen species while their photodegradation products were not responsible for their activity. The most active compounds exhibited photocytotoxicity with IC(50) values at low micromolar level inducing a decrease in the intracellular content of thiol, thus triggering cancer cell death through apoptosis. All the pyridone derivatives revealed to be pure photosensitizers with preferential photocytotoxic activity towards cancerous over healthy cells. Altogether, the results obtained confirm pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones as promising photosensitisers against triple-negative breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12272-022-01414-1.