Ru(III) complexes with lonidamine-modified ligands

A series of bifunctional Ru(III) complexes with lonidamine-modified ligands (lonidamine is a selective inhibitor of aerobic glycolysis in cancer cells) was described. Redox properties of Ru(III) complexes were characterized by cyclic voltammetry. An easy reduction suggested a perspective for these agents as their whole mechanism of action seems to be based on activation by metal atom reduction. New compounds demonstrated a more pronounced antiproliferative potency than the parental drug; individual new agents were more cytotoxic than cisplatin. Stability studies showed an increase in the stability of complexes along with the linker length. A similar trend was noted for antiproliferative activity, cellular uptake, apoptosis induction, and thioredoxin reductase inhibition. Finally, at concentrations that did not alter water solubility, the selected new complex evoked no acute toxicity in Balb/c mice. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Авторы
Shutkov I.A.1 , Okulova Y.N.1 , Tyurin V.Yu.1 , Sokolova E.V.2 , Babkov D.A.2 , Spasov A.A.2 , Gracheva Y.A.1 , Schmidt C.3 , Kirsanov K.I. 4, 5 , Shtil A.A. 4 , Redkozubova O.M.6 , Shevtsova E.F.7 , Milaeva E.R.1 , Ott I.3 , Nazarov A.A. 1
Издательство
MDPI AG
Номер выпуска
24
Язык
Английский
Статус
Опубликовано
Номер
13468
Том
22
Год
2021
Организации
  • 1 Department of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, Moscow, 119991, Russian Federation
  • 2 Scientific Center for Innovative Drugs, Volgograd State Medical University, 39 Novorossiyskaya Street, Volgograd, 400087, Russian Federation
  • 3 Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, 55 Beethovenstrasse, Braunschweig, 38106, Germany
  • 4 Blokhin Cancer Research Center, 24 Kashirskoye Shosse, Moscow, 115478, Russian Federation
  • 5 Institute of Medicine, RUDN University, 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
  • 6 Neurobotics, Zelenograd pas. 4922, 4-2-477, Moscow, 124498, Russian Federation
  • 7 Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severniy Proezd, Chernogolovka, 142432, Russian Federation
Ключевые слова
Antiproliferative activity; Cell death; Lonidamine; Redox balance; Thioredoxin reductase
Дата создания
06.07.2022
Дата изменения
06.07.2022
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/84495/
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