New Derivatives of Bacteriopurpurin with Thiolated Au (I) Complexes: Dual Darkand Light Activated Antitumor Potency.
| Title: | New Derivatives of Bacteriopurpurin with Thiolated Au (I) Complexes: Dual Darkand Light Activated Antitumor Potency. |
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| Authors: | Grin MA; MIREA - Russian Technological University, Moscow, Russian Federation.; Tikhonov SI; MIREA - Russian Technological University, Moscow, Russian Federation.; Petrova AS; RUDN University, Moscow, Russian Federation.; Pogorilyy VA; MIREA - Russian Technological University, Moscow, Russian Federation.; Noev АN; MIREA - Russian Technological University, Moscow, Russian Federation.; Tatarskiy VV; Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation.; Shpakovsky DB; Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, Russian Federation.; Milaeva ER; Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, Russian Federation.; Kalinina EV; RUDN University, Moscow, Russian Federation.; Chernov NN; RUDN University, Moscow, Russian Federation.; Shtil АА; Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation.; Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, Russian Federation.; Mironov AF; MIREA - Russian Technological University, Moscow, Russian Federation.; Kaprin AD; National Medical Research Center of Radiology of Ministry of Health of Russia, Moscow, Russian Federation.; Filonenko EV; National Medical Research Center of Radiology of Ministry of Health of Russia, Moscow, Russian Federation. |
| Source: | Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2020; Vol. 20 (1), pp. 49-58. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Bentham Science Publishers Country of Publication: Netherlands NLM ID: 101265649 Publication Model: Print Cited Medium: Internet ISSN: 1875-5992 (Electronic) Linking ISSN: 18715206 NLM ISO Abbreviation: Anticancer Agents Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Bentham Science Publishers; Original Publication: Sharjah, U.A.E. ; San Francisco, CA : Bentham Science Publishers, [2006]- |
| MeSH Terms: | Light*; Antineoplastic Agents/*pharmacology ; Gold/*pharmacology ; Organogold Compounds/*pharmacology ; Pheophytins/*pharmacology ; Sulfhydryl Compounds/*pharmacology; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Cell Death/drug effects ; Gold/chemistry ; Organogold Compounds/chemical synthesis ; Organogold Compounds/chemistry ; Pheophytins/chemistry ; Sulfhydryl Compounds/chemistry ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; HCT116 Cells ; Humans ; Molecular Structure ; Structure-Activity Relationship ; Tumor Cells, Cultured |
| Abstract: | 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.; (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| Contributed Indexing: | Keywords: Au (I) thiolates; Bacteriopurpurin; photodynamic therapy; photonecrosis; photosensitizers; tumor cells. |
| Substance Nomenclature: | 0 (Antineoplastic Agents); 0 (Organogold Compounds); 0 (Pheophytins); 0 (Sulfhydryl Compounds); 17453-58-6 (bacteriopheophytin); 7440-57-5 (Gold) |
| Entry Date(s): | Date Created: 20190802 Date Completed: 20210106 Latest Revision: 20210106 |
| Update Code: | 20260130 |
| DOI: | 10.2174/1871520619666190801102617 |
| PMID: | 31368879 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't