19个吡咯并[1,2-h][1,7]萘啉酮和吡啶并[2,3-c]吡咯并[1,2-a]氮杂烷酮被合成为一个新的三环系统，在该系统中，吡啶环被附加到6,7-二氢吲哚噻唑-8(5H)-酮和5,6,7,8-四氢-9H-嘧啶并[1,2-a]氮杂烷-9-酮基团上，以获得潜在的光敏剂。它们经过暗处和紫外线A光(2.0 J/cm2)下的光抗增殖活性测试，以对三阴性乳腺癌细胞系MDA-MB-231的影响。我们证明，它们的毒性仅在受光照射时，主要是由于产生的活性氧物种，而它们的光降解产物不负责它们的活性。最活性的化合物表现出低微摩尔级的光细胞毒性(IC50值)，通过诱导巯基内细胞内容物的减少而触发细胞凋亡。所有的吡啶酮衍生物均表现出纯粹的光敏感性，并对癌细胞优先显示光细胞毒性活性。总之，所获得的结果证实了吡咯并[1,2-h][1,7]萘啉酮和吡啶并[2,3-c]吡咯并[1,2-a]氮杂烷酮是有前途的用于三阴性乳腺癌的光敏剂。© 2022年。作者(们)。

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.© 2022. The Author(s).