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 a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13468 |
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| author | Ilya A. Shutkov Yulia N. Okulova Vladimir Yu. Tyurin Elena V. Sokolova Denis A. Babkov Alexander A. Spasov Yulia A. Gracheva Claudia Schmidt Kirill I. Kirsanov Alexander A. Shtil Olga M. Redkozubova Elena F. Shevtsova Elena R. Milaeva Ingo Ott Alexey A. Nazarov |
| author_facet | Ilya A. Shutkov Yulia N. Okulova Vladimir Yu. Tyurin Elena V. Sokolova Denis A. Babkov Alexander A. Spasov Yulia A. Gracheva Claudia Schmidt Kirill I. Kirsanov Alexander A. Shtil Olga M. Redkozubova Elena F. Shevtsova Elena R. Milaeva Ingo Ott Alexey A. Nazarov |
| author_sort | Ilya A. Shutkov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:55:36Z |
| format | Article |
| id | doaj.art-66d5edea20494582a053ff3482bda224 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:55:36Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-66d5edea20494582a053ff3482bda2242023-11-23T08:46:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241346810.3390/ijms222413468Ru(III) Complexes with Lonidamine-Modified LigandsIlya A. Shutkov0Yulia N. Okulova1Vladimir Yu. Tyurin2Elena V. Sokolova3Denis A. Babkov4Alexander A. Spasov5Yulia A. Gracheva6Claudia Schmidt7Kirill I. Kirsanov8Alexander A. Shtil9Olga M. Redkozubova10Elena F. Shevtsova11Elena R. Milaeva12Ingo Ott13Alexey A. Nazarov14Department of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaDepartment of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaDepartment of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaScientific Center for Innovative Drugs, Volgograd State Medical University, 39 Novorossiyskaya Street, 400087 Volgograd, RussiaScientific Center for Innovative Drugs, Volgograd State Medical University, 39 Novorossiyskaya Street, 400087 Volgograd, RussiaScientific Center for Innovative Drugs, Volgograd State Medical University, 39 Novorossiyskaya Street, 400087 Volgograd, RussiaDepartment of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaInstitute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, 55 Beethovenstrasse, 38106 Braunschweig, GermanyBlokhin Cancer Research Center, 24 Kashirskoye Shosse, 115478 Moscow, RussiaBlokhin Cancer Research Center, 24 Kashirskoye Shosse, 115478 Moscow, RussiaNeurobotics, Zelenograd pas. 4922, 4-2-477, 124498 Moscow, RussiaInstitute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severniy Proezd, 142432 Chernogolovka, RussiaDepartment of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaInstitute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, 55 Beethovenstrasse, 38106 Braunschweig, GermanyDepartment of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaA 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.https://www.mdpi.com/1422-0067/22/24/13468lonidamineredox balancecell deathantiproliferative activitythioredoxin reductase |
| spellingShingle | Ilya A. Shutkov Yulia N. Okulova Vladimir Yu. Tyurin Elena V. Sokolova Denis A. Babkov Alexander A. Spasov Yulia A. Gracheva Claudia Schmidt Kirill I. Kirsanov Alexander A. Shtil Olga M. Redkozubova Elena F. Shevtsova Elena R. Milaeva Ingo Ott Alexey A. Nazarov Ru(III) Complexes with Lonidamine-Modified Ligands International Journal of Molecular Sciences lonidamine redox balance cell death antiproliferative activity thioredoxin reductase |
| title | Ru(III) Complexes with Lonidamine-Modified Ligands |
| title_full | Ru(III) Complexes with Lonidamine-Modified Ligands |
| title_fullStr | Ru(III) Complexes with Lonidamine-Modified Ligands |
| title_full_unstemmed | Ru(III) Complexes with Lonidamine-Modified Ligands |
| title_short | Ru(III) Complexes with Lonidamine-Modified Ligands |
| title_sort | ru iii complexes with lonidamine modified ligands |
| topic | lonidamine redox balance cell death antiproliferative activity thioredoxin reductase |
| url | https://www.mdpi.com/1422-0067/22/24/13468 |
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