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Novel Copper-Containing Cytotoxic Agents Based on 2-Thioxoimidazolones.
Krasnovskaya, Olga O; Guk, Dmitry A; Naumov, Alexey E; Nikitina, Vita N; Semkina, Alevtina S; Vlasova, Kseniya Yu; Pokrovsky, Vadim; Ryabaya, Oksana O; Karshieva, Saida S; Skvortsov, Dmitry A; Zhirkina, Irina V; Shafikov, Radik R; Gorelkin, Petr V; Vaneev, Alexander N; Erofeev, Alexander S; Mazur, Dmitrii M; Tafeenko, Viktor A; Pergushov, Vladimir I; Melnikov, Mikhail Ya; Soldatov, Mikhail A; Shapovalov, Victor V; Soldatov, Alexander V; Akasov, Roman A; Gerasimov, Vasily M; Sakharov, Dmitry A; Moiseeva, Anna A; Zyk, Nikolay V; Beloglazkina, Elena K; Majouga, Alexander G.
Affiliation
  • Krasnovskaya OO; Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology MISIS, Leninskiy Prospect 4, Moscow 101000, Russia.
  • Guk DA; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Naumov AE; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Nikitina VN; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Semkina AS; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Vlasova KY; Department of Medical Nanobiotechnologies, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia.
  • Pokrovsky V; Department of Basic and Applied Neurobiology, Serbsky National Medical Research Center for Psychiatry and Narcology, Kropotkinskiy 23, Moscow 119991, Russia.
  • Ryabaya OO; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Karshieva SS; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Kashirskoe Highway 23, Moscow 115478, Russia.
  • Skvortsov DA; People's Friendship University, Moscow, Russia, Miklukho-Maklaya 6, Moscow 117198, Russia.
  • Zhirkina IV; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Kashirskoe Highway 23, Moscow 115478, Russia.
  • Shafikov RR; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Kashirskoe Highway 23, Moscow 115478, Russia.
  • Gorelkin PV; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Vaneev AN; Department of Biology and Biotechnologies, Higher School of Economics, Myasnitskaya 13, Moscow 101000, Russia.
  • Erofeev AS; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Mazur DM; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Tafeenko VA; Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology MISIS, Leninskiy Prospect 4, Moscow 101000, Russia.
  • Pergushov VI; Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology MISIS, Leninskiy Prospect 4, Moscow 101000, Russia.
  • Melnikov MY; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Soldatov MA; Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology MISIS, Leninskiy Prospect 4, Moscow 101000, Russia.
  • Shapovalov VV; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Soldatov AV; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Akasov RA; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Gerasimov VM; Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow 119991, Russia.
  • Sakharov DA; The Smart Materials Research Institute Southern Federal University Sladkova, 178/24, Rostov-on-Don 344090, Russia.
  • Moiseeva AA; The Smart Materials Research Institute Southern Federal University Sladkova, 178/24, Rostov-on-Don 344090, Russia.
  • Zyk NV; The Smart Materials Research Institute Southern Federal University Sladkova, 178/24, Rostov-on-Don 344090, Russia.
  • Beloglazkina EK; Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology MISIS, Leninskiy Prospect 4, Moscow 101000, Russia.
  • Majouga AG; I.M. Sechenov First Moscow State Medical University, Trubetskaya 8-2, Moscow 119991, Russia.
J Med Chem ; 63(21): 13031-13063, 2020 11 12.
Article in En | MEDLINE | ID: mdl-32985193
A series of 73 ligands and 73 of their Cu+2 and Cu+1 copper complexes with different geometries, oxidation states of the metal, and redox activities were synthesized and characterized. The aim of the study was to establish the structure-activity relationship within a series of analogues with different substituents at the N(3) position, which govern the redox potentials of the Cu+2/Cu+1 redox couples, ROS generation ability, and intracellular accumulation. Possible cytotoxicity mechanisms, such as DNA damage, DNA intercalation, telomerase inhibition, and apoptosis induction, have been investigated. ROS formation in MCF-7 cells and three-dimensional (3D) spheroids was proven using the Pt-nanoelectrode. Drug accumulation and ROS formation at 40-60 µm spheroid depths were found to be the key factors for the drug efficacy in the 3D tumor model, governed by the Cu+2/Cu+1 redox potential. A nontoxic in vivo single-dose evaluation for two binuclear mixed-valence Cu+1/Cu+2 redox-active coordination compounds, 72k and 61k, was conducted.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Copper / Coordination Complexes / Imidazoles Type of study: Prognostic_studies Limits: Humans Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2020 Type: Article Affiliation country: Russia
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Copper / Coordination Complexes / Imidazoles Type of study: Prognostic_studies Limits: Humans Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2020 Type: Article Affiliation country: Russia