Mitochondria-targeting indolizino[3,2-c]quinolines as novel class of photosensitizers for photodynamic anticancer activity

Soonbum Kwon, Yeongcheol Lee, Youngeun Jung, Ju Hee Kim, Byungyeob Baek, Bumhee Lim, Jungeun Lee, Ikyon Kim, Jeeyeon Lee

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

To achieve efficient photodynamic activity, substantial effort has been dedicated to precise control of the intracellular localization of current photosensitizers (PSs). Given the extremely small radius of action of singlet oxygen, the direct targeting of PSs to the mitochondria is expected to greatly enhance the photodynamic therapy (PDT) activity. Here, we report mitochondria-targeting 6-(furan-2-yl)- and 6-(thiophen-2-yl) indolizino[3,2-c]quinolines (IQs) as novel PSs. IQ derivatives containing 5-membered heterocyclic aromatic rings were synthesized, and their photophysical properties as PSs were characterized. The anticancer potentials of 2a-2f were investigated using various cancer cell lines, and they exhibited dose-dependent and light exposure time-dependent cytotoxicity. Among the synthesized compounds, 2b, which contains a furan ring, showed dual functions as an imaging probe as well as a PS. Real-time confocal fluorescence images revealed the mitochondrial localization of 2b as a primary site of photodamage in live cells. Targeted reactive oxygen species (ROS)-generation capabilities and the photoinduced DNA cleavage of IQs led to mitochondrial dysfunction and photoinduced apoptosis via the intrinsic pathway. 3D RI tomograms of individual live HeLa cells treated with 2b showed that the progress of photoinduced apoptosis was affected by the PS concentration and light irradiation time. The studied IQs (2b, 2d, and 2e) are expected to serve as a new class of heavy-atom-free PSs with low molecular weights less than 350.

Original languageEnglish
Pages (from-to)116-127
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume148
DOIs
Publication statusPublished - 2018 Mar 25

Fingerprint

Quinolines
Mitochondria
Photosensitizing Agents
Apoptosis
Light
Singlet Oxygen
DNA Cleavage
Photodynamic therapy
Photochemotherapy
Cytotoxicity
HeLa Cells
Dosimetry
Reactive Oxygen Species
Molecular Weight
Fluorescence
Molecular weight
Cells
Irradiation
Derivatives
Imaging techniques

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Kwon, Soonbum ; Lee, Yeongcheol ; Jung, Youngeun ; Kim, Ju Hee ; Baek, Byungyeob ; Lim, Bumhee ; Lee, Jungeun ; Kim, Ikyon ; Lee, Jeeyeon. / Mitochondria-targeting indolizino[3,2-c]quinolines as novel class of photosensitizers for photodynamic anticancer activity. In: European Journal of Medicinal Chemistry. 2018 ; Vol. 148. pp. 116-127.
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Mitochondria-targeting indolizino[3,2-c]quinolines as novel class of photosensitizers for photodynamic anticancer activity. / Kwon, Soonbum; Lee, Yeongcheol; Jung, Youngeun; Kim, Ju Hee; Baek, Byungyeob; Lim, Bumhee; Lee, Jungeun; Kim, Ikyon; Lee, Jeeyeon.

In: European Journal of Medicinal Chemistry, Vol. 148, 25.03.2018, p. 116-127.

Research output: Contribution to journalArticle

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AU - Kwon, Soonbum

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