2. Academic Validation
  3. Ru(III) Complexes with Lonidamine-Modified Ligands

Ru(III) Complexes with Lonidamine-Modified Ligands

  • Int J Mol Sci. 2021 Dec 15;22(24):13468. doi: 10.3390/ijms222413468.
Ilya A Shutkov 1,  Yulia N Okulova 1,  Vladimir Yu Tyurin 1,  Elena V Sokolova 2,  Denis A Babkov 2,  Alexander A Spasov 2,  Yulia A Gracheva 1,  Claudia Schmidt 3,  Kirill I Kirsanov 4 5,  Alexander A Shtil 4,  Olga M Redkozubova 6,  Elena F Shevtsova 7,  Elena R Milaeva 1,  Ingo Ott 3,  Alexey A Nazarov 1
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, Russia.
  • 2 Scientific Center for Innovative Drugs, Volgograd State Medical University, 39 Novorossiyskaya Street, 400087 Volgograd, Russia.
  • 3 Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, 55 Beethovenstrasse, 38106 Braunschweig, Germany.
  • 4 Blokhin Cancer Research Center, 24 Kashirskoye Shosse, 115478 Moscow, Russia.
  • 5 Institute of Medicine, RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia.
  • 6 Neurobotics, Zelenograd pas. 4922, 4-2-477, 124498 Moscow, Russia.
  • 7 Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severniy Proezd, 142432 Chernogolovka, Russia.
PMID: 34948263 DOI: 10.3390/ijms222413468
Abstract

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.

Keywords

antiproliferative activity; cell death; lonidamine; redox balance; thioredoxin reductase.

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