β-Maleimide substituted meso-arylporphyrins: Synthesis, transformations, physico-chemical and antitumor properties

The maleimide moiety is widely used in drug design. To explore the properties of maleimide containing photosensitizers we obtained a series of new β-maleimide functionalized meso-arylporphyrins through acylation of β-amino group in porphyrins with maleic anhydride followed by condensation of maleic acid monoamides. The selective reactivity of porphyrin maleimides toward thiols was demonstrated using mercaptocarboranes and cysteine. New derivatives retained the ability of tetrapyrrolic macrocyclic compounds to absorb light in visible spectral region and to generate triplet states and reactive oxygen species upon photoactivation. Importantly, illumination of cells loaded with a cell permeable 2-{3-[(o-carboran-1′-yl)thio]pyrrolidine-2,5-dione-1-yl}-5,10,15,20-tetraphenylporphyrin triggered rapid (within the initial minutes) generation of superoxide anion radical concomitantly with a decrease of mitochondrial membrane potential, and then the loss of the plasma membrane integrity and cell death. Thus, the maleimide-substituted porphyrins represent a new chemotype of polyfunctionalized compounds for an in-depth investigation as photosensitizers in cancer and beyond. © 2019

Authors
Ol'shevskaya V.A. 1 , Alpatova V.M.1, 2 , Radchenko A.S.3 , Ramonova A.A.4 , Petrova A.S. 5 , Tatarskiy V.V. 6, 7, 8 , Zaitsev A.V. 1 , Kononova E.G.1 , Ikonnikov N.S. 1 , Kostyukov A.A.3 , Egorov A.E.3 , Moisenovich M.M.4 , Kuzmin V.A.3 , Bragina N.A.2 , Shtil A.A. 6, 7
Publisher
Elsevier Ltd
Language
English
Status
Published
Number
107760
Volume
171
Year
2019
Organizations
  • 1 A.N.Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991, Russian Federation
  • 2 MIREA - Russian Technological University, M.V. Lomonosov Institute of Fine Chemical Technologies, Moscow, 119571, Russian Federation
  • 3 Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334, Russian Federation
  • 4 Department of Biology, Moscow State University, Moscow, 119991, Russian Federation
  • 5 RUDN University, Moscow, 117198, Russian Federation
  • 6 Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russian Federation
  • 7 Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russian Federation
  • 8 National University of Science and Technology “MISIS”, Moscow, 119991, Russian Federation
Keywords
Carboranes; Fluorescence; Maleimides; Phototoxicity; Porphyrins; Singlet oxygen
Date of creation
24.12.2019
Date of change
24.12.2019
Short link
https://repository.rudn.ru/en/records/article/record/54844/
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