Synthesis and Investigation of Photophysical and Biological Properties of Novel S-Containing Bacteriopurpurinimides
| Autor: | Anna V. Starovoitova, G. I. Filkov, P.V. Ostroverkhov, Yuri S. Romanko, Vadim V. Yuzhakov, Nelli.V. Burmistrova, Andrey F. Mironov, Anastasiya A. Ignatova, Anatoliy A. Tsigankov, Tatyana Karmakova, Yan A. Ivanenkov, Maxim A. Abakumov, Alexander G. Majouga, Ivan V. Pantushenko, E. A. Plotnikova, Mikhail A. Kaplan, Alexey V. Feofanov, M. A. Grin, Raisa I. Yakubovskaya |
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| Rok vydání: | 2017 |
| Předmět: |
Porphyrins
Chemistry Techniques Synthetic 010402 general chemistry 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine In vivo Cell Line Tumor Drug Discovery Moiety Molecule Animals Tissue Distribution Disulfides Photosensitizing Agents Singlet Oxygen Chemistry Singlet oxygen Glutathione Fluorescence Combinatorial chemistry In vitro 0104 chemical sciences Rats Photochemotherapy 030220 oncology & carcinogenesis Molecular Medicine Administration Intravenous Female Sarcoma Experimental Intracellular |
| Zdroj: | Journal of medicinal chemistry. 60(24) |
| ISSN: | 1520-4804 |
| Popis: | Novel hybrid molecule containing 2-mercaptoethylamine was synthesized starting from O-propyloxime-N-propoxy bacteriopurpurinimide (dipropoxy-BPI), which was readily oxidized in oxygen atmosphere yielding the corresponding disulfide analogue (disulfide-BPI). Spectral, photophysical, photodynamic, and biological properties of compound were properly evaluated. Compounds bearing disulfide moiety can directly interact with glutathione (GSH), thereby reducing its intracellular concentration. Indeed, mice sarcoma S37 cell line was treated in vitro with disulfide-BPI, yielding a CC50 value of 0.05 ± 0.005 μM. A relatively high level of singlet oxygen was detected. It was demonstrated (by fluorescence) that the PS was rapidly accumulated in a cancer nest (S37) at a relatively high level after 2 h upon intravenous administration. After 24 h, no traces of the molecule were detected in the tumor mass. Moreover, high photodynamic efficiency was demonstrated at doses of 150-300 J/cm2 against two different in vivo tumor models, achieving 100% regression of cancer growth. |
| Databáze: | OpenAIRE |
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