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KMID : 0043320220450110806
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Archives of Pharmacal Research
2022 Volume.45 No. 11 p.806 ~ p.821
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New tricyclic systems as photosensitizers towards triple negative breast cancer cells
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Barreca Marilia
Angela Maria Ingarra
Raimondi Maria Valeria
Spano Virginia
Piccionello Antonio Palumbo
Franco Michele De
Menilli Luca
Gandin Valentina
Miolo Giorgia
Barraja Paola
Montalbano Alessandra
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Abstract
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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/cm2). 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 IC50 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.
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KEYWORD
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MDA-MB-231, Photosensitizing agents, Phototoxic activity, Pyrido[2,3-c]pyrrolo[1,2-a]azepinone, Pyrrolo[1,2-h][1,7]naphthyridinone, Triple-negative breast cancer.
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