New derivatives of bacteriopurpurin with thiolated au (I) complexes: Dual dark-and light activated antitumor potency

Background: Conventional antitumor Photosensitizers (PS) are normally low toxic in the dark whereas light activation triggers massive cell death (photodynamic therapy, PDT). Objective: To expand the therapeutic potential of PS to dual potency cytocidal agents, taking advantage of the use of bacteriopurpurin for a deeper tissue penetration of light, and suitability of the tetrapyrrolic macrocycle for chemical modifications at its periphery. Methods: Conjugation of a pro-oxidant thiolate Au (I) moiety to the bacteriopurpurin core and evaluation of cytotoxicity in cell culture and in vivo. Results: New water-soluble derivatives showed micromolar cytotoxicity for cultured human tumor cell lines in the dark, including the subline with an altered drug response due to p53 inactivation. Cellular PDT with the selected conjugate, thiolate Au (I)-dipropoxybacteriopurpurinimide (compound 6) with two triphenylphosphine Au fragments, triggered rapid (within minutes) cell death. Damage to the plasma membrane (necrosis) was a hallmark of cell death by compound 6 both in the dark and upon light activation. Furthermore, one single i.v. injection of compound 6 caused retardation of transplanted syngeneic tumors at the tolerable dose. Illumination of tumors that accumulated compound 6 significantly synergized with the effect of 6 in the dark. Conclusion: Complexes of virtually non-toxic, photoactivatable bacteriopurpurin with the gold-containing organic moiety are considered the dual potency antitumor agents, tentatively applicable for intractable tumors. © 2020 Bentham Science Publishers.

Authors
Grin M.A.1 , Tikhonov S.I.1 , Petrova A.S. 2 , Pogorilyy V.A.1 , Noev А.N.1 , Tatarskiy V.V. 3 , Shpakovsky D.B.4 , Milaeva E.R.4 , Kalinina E.V. 2 , Chernov N.N. 2 , Shtil А.А.3, 4 , Mironov A.F.1 , Kaprin A.D. 5 , Filonenko E.V. 5
Publisher
Bentham Science Publishers
Number of issue
1
Language
English
Pages
49-58
Status
Published
Volume
20
Year
2020
Organizations
  • 1 MIREA-Russian Technological University, Moscow, Russian Federation
  • 2 RUDN University, Moscow, Russian Federation
  • 3 Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation
  • 4 Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, Russian Federation
  • 5 National Medical Research Center of Radiology of Ministry of Health of Russia, Moscow, Russian Federation
Keywords
Au (I) thiolates; Bacteriopurpurin; Photodynamic therapy; Photonecrosis; Photosensitizers; Tumor cells
Date of creation
02.11.2020
Date of change
02.11.2020
Short link
https://repository.rudn.ru/en/records/article/record/65641/
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