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Photophysical Properties of Emissive Pyrido[3,2‐ c ]carbazole Derivatives and Apoptosis Induction: Development towards Theranostic Agents in Response to Light Stimulus
Author(s) -
Sakuma Masaomi,
Fuchi Yasufumi,
Usui Kazuteru,
Karasawa Satoru
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201901200
Subject(s) - hela , carbazole , cytotoxicity , chemistry , apoptosis , fluorescence , tertiary amine , biophysics , photochemistry , biochemistry , cell , biology , in vitro , organic chemistry , physics , quantum mechanics
Pyridocarbazole moieties are present in many natural products, such as olivacine and ellipticine, and their derivatives are well‐known anticancer agents. To develop functional therapeutic and diagnostic compounds, three emissive pyrido[3,2‐ c ]carbazole derivatives, PC‐X , containing secondary or tertiary amine groups, were synthesized from an aminoquinoline derivative using a palladium complex as the catalyst. X‐ray diffraction analyses revealed that PC‐X showed highly planar structures between the pyridine ring and the carbazole framework, exhibiting high fluorescence intensities along with solvatochromic behavior. Imaging of HeLa cells treated with PC‐X showed no specific accumulation into the organelles; however, a comparative examination showed that the accumulation in mitochondria was the highest as compared to nuclei and lysosomes. Cytotoxicity analysis using HeLa cells showed that PC‐H, containing a secondary amine group showed the highest cytotoxicity (IC 50 ≈20 μ m ) as compared to another PC‐X having a tertiary amine group. Colocalization with MitoTracker, a typical mitochondrial staining dye, showed apoptosis‐like behavior with remarkable appearance of blebbing during irradiation with near UV light (403 nm), suggesting that the PC‐H may not only behave as a fluorescence probe for the imaging organelles, but also as a therapeutic agent for inducing apoptosis in HeLa cells, thereby functioning as a theranostic agent.