Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus
The high prevalence of type 2 diabetes mellitus (T2DM), and the lack of effective therapy, determine the need for new treatment options. The present study is focused on the NO-donors drug class as effective antidiabetic agents. Since numerous biological systems are involved in the pathogenesis and p...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/13/7/615 |
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| author | Irina I. Faingold Yuliya V. Soldatova Darya A. Poletaeva Elena N. Klimanova Nataliya A. Sanina |
| author_facet | Irina I. Faingold Yuliya V. Soldatova Darya A. Poletaeva Elena N. Klimanova Nataliya A. Sanina |
| author_sort | Irina I. Faingold |
| collection | DOAJ |
| description | The high prevalence of type 2 diabetes mellitus (T2DM), and the lack of effective therapy, determine the need for new treatment options. The present study is focused on the NO-donors drug class as effective antidiabetic agents. Since numerous biological systems are involved in the pathogenesis and progression of T2DM, the most promising approach to the development of effective drugs for the treatment of T2DM is the search for pharmacologically active compounds that are selective for a number of therapeutic targets for T2DM and its complications: oxidative stress, non-enzymatic protein glycation, polyol pathway. The nitrosyl iron complex with thiosulfate ligands was studied in this work. Binuclear iron nitrosyl complexes are synthetic analogues of [2Fe–2S] centers in the regulatory protein natural reservoirs of NO. Due to their ability to release NO without additional activation under physiological conditions, these compounds are of considerable interest for the development of potential drugs. The present study explores the effects of tetranitrosyl iron complex with thiosulfate ligands (TNIC-ThS) on T2DM and its complications regarding therapeutic targets in vitro, as well as its ability to bind liposomal membrane, inhibit lipid peroxidation (LPO), and non-enzymatic glycation of bovine serum albumin (BSA), as well as aldose reductase, the enzyme that catalyzes the reduction in glucose to sorbitol in the polyol pathway. Using the fluorescent probe method, it has been shown that TNIC-ThS molecules interact with both hydrophilic and hydrophobic regions of model membranes. TNIC-ThS inhibits lipid peroxidation, exhibiting antiradical activity due to releasing NO (IC50 = 21.5 ± 3.7 µM). TNIC-ThS was found to show non-competitive inhibition of aldose reductase with Ki value of 5.25 × 10<sup>−4</sup> M. In addition, TNIC-ThS was shown to be an effective inhibitor of the process of non-enzymatic protein glycation in vitro (IC50 = 47.4 ± 7.6 µM). Thus, TNIC-ThS may be considered to contribute significantly to the treatment of T2DM and diabetic complications. |
| first_indexed | 2024-03-11T00:50:36Z |
| format | Article |
| id | doaj.art-29e28cf0e55748f7a3a87c4417b18f51 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-11T00:50:36Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-29e28cf0e55748f7a3a87c4417b18f512023-11-18T20:25:49ZengMDPI AGMembranes2077-03752023-06-0113761510.3390/membranes13070615Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes MellitusIrina I. Faingold0Yuliya V. Soldatova1Darya A. Poletaeva2Elena N. Klimanova3Nataliya A. Sanina4Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Academician Semenov Avenue 1, Chernogolovka 142432, RussiaFederal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Academician Semenov Avenue 1, Chernogolovka 142432, RussiaFederal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Academician Semenov Avenue 1, Chernogolovka 142432, RussiaFederal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Academician Semenov Avenue 1, Chernogolovka 142432, RussiaFederal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Academician Semenov Avenue 1, Chernogolovka 142432, RussiaThe high prevalence of type 2 diabetes mellitus (T2DM), and the lack of effective therapy, determine the need for new treatment options. The present study is focused on the NO-donors drug class as effective antidiabetic agents. Since numerous biological systems are involved in the pathogenesis and progression of T2DM, the most promising approach to the development of effective drugs for the treatment of T2DM is the search for pharmacologically active compounds that are selective for a number of therapeutic targets for T2DM and its complications: oxidative stress, non-enzymatic protein glycation, polyol pathway. The nitrosyl iron complex with thiosulfate ligands was studied in this work. Binuclear iron nitrosyl complexes are synthetic analogues of [2Fe–2S] centers in the regulatory protein natural reservoirs of NO. Due to their ability to release NO without additional activation under physiological conditions, these compounds are of considerable interest for the development of potential drugs. The present study explores the effects of tetranitrosyl iron complex with thiosulfate ligands (TNIC-ThS) on T2DM and its complications regarding therapeutic targets in vitro, as well as its ability to bind liposomal membrane, inhibit lipid peroxidation (LPO), and non-enzymatic glycation of bovine serum albumin (BSA), as well as aldose reductase, the enzyme that catalyzes the reduction in glucose to sorbitol in the polyol pathway. Using the fluorescent probe method, it has been shown that TNIC-ThS molecules interact with both hydrophilic and hydrophobic regions of model membranes. TNIC-ThS inhibits lipid peroxidation, exhibiting antiradical activity due to releasing NO (IC50 = 21.5 ± 3.7 µM). TNIC-ThS was found to show non-competitive inhibition of aldose reductase with Ki value of 5.25 × 10<sup>−4</sup> M. In addition, TNIC-ThS was shown to be an effective inhibitor of the process of non-enzymatic protein glycation in vitro (IC50 = 47.4 ± 7.6 µM). Thus, TNIC-ThS may be considered to contribute significantly to the treatment of T2DM and diabetic complications.https://www.mdpi.com/2077-0375/13/7/615nitric oxidenitrosyl iron complexesmodel membraneliposomesmembranotropic propertiesanti-glycation activity |
| spellingShingle | Irina I. Faingold Yuliya V. Soldatova Darya A. Poletaeva Elena N. Klimanova Nataliya A. Sanina Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus Membranes nitric oxide nitrosyl iron complexes model membrane liposomes membranotropic properties anti-glycation activity |
| title | Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus |
| title_full | Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus |
| title_fullStr | Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus |
| title_full_unstemmed | Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus |
| title_short | Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus |
| title_sort | influence of nitrosyl iron complex with thiosulfate ligands on therapeutically important targets related to type 2 diabetes mellitus |
| topic | nitric oxide nitrosyl iron complexes model membrane liposomes membranotropic properties anti-glycation activity |
| url | https://www.mdpi.com/2077-0375/13/7/615 |
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