Russian Journal of Bioorganic Chemistry最新文献

{"title":"Porphyrins as Polyfunctional Ligands for Binding to DNA. Prospects for Application (A Review)","authors":"N. Sh. Lebedeva,&nbsp;E. S. Yurina","doi":"10.1134/S1068162024060360","DOIUrl":"10.1134/S1068162024060360","url":null,"abstract":"<p>The study of the interaction of nucleic acids with ligands is relevant both in terms of scientific interest and high potential practical significance. Nucleic acid complex formation with ligands affects the biochemical functions of the most important carrier of genetic information, which opens up opportunities for treating genetic diseases and controlling the aging of both cells and the organism as a whole. Among the huge variety of potential ligands, porphyrins and related compounds occupy a special placedue to their ability to generate reactive oxygen species under irradiation with light. The photocatalytic properties of porphyrins can be used in the creation of molecular tools for genetic engineering and the treatment of viral and bacterial infections at the genetic level. Modification of porphyrin compounds allows targeting of the ligand to a specific biological target.The review summarizes the literature data describing the process of nucleic acid complex formation with aromatic ligands, mainly with porphyrins. The influence of the structure of macroheterocycles on the features of interaction with nucleic acids is analyzed. Promising directions for further research are outlined.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2567 - 2579"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptation of the Protocol of the Automated Solid-Phase Phosphoramidite Synthesis of Oligodeoxyribonucleotides for Preparing Their N-Unsubstituted Phosphoramidate Analogs (P–NH2)","authors":"E. A. Malova,&nbsp;I. A. Pyshnaya,&nbsp;M. I. Meschaninova,&nbsp;D. V. Pyshnyi","doi":"10.1134/S106816202406027X","DOIUrl":"10.1134/S106816202406027X","url":null,"abstract":"<p><b>Objective:</b> The systematic use of P–NH₂ analogs of nucleic acids as objects and/or tools in molecular biology and biomedicine is limited by the complexity of their synthesis. For almost 40 years, researchers have been looking for effective synthetic approaches to P–NH₂ oligonucleotides. These analogs, which are isostructurally identical to natural oligonucleotides, have not been further developed even though a lot of publications on their synthesis and characteristics. To develop a more straightforward and cost-effective method than those being practiced today, our group set out to modify the phosphoramidite protocol of oligonucleotide (ON) synthesis for preparing the P–NH₂ analogs of oligodeoxyribonucleotides. <b>Methods:</b> For the synthesis of the P–NH₂ analogs, a standard, presently widely used protocol of the phosphoramidite synthesis of oligonucleotides was taken as a basis. The P–NH₂ modification was introduced at the oxidation step <i>via</i> the Staudinger reaction, using (9-fluorenyl)methoxycarbonyl azide (FmocN₃). The subsequent formation of an <i>N</i>-unsubstituted phosphoramidate moiety in the oligonucleotide was accomplished by the removal of the Fmoc group by treatment with a strong base. The thermodynamic properties of the P–NH₂ analogs as part of complementary nucleic acid complexes formed in low-ionic-strength solutions were studied by thermal denaturation analysis with optical signal registration. <b>Results and Discussion:</b> It was found that to increase the efficiency of synthesis of electroneutral P–NH₂ oligonucleotides additional Fmoc cleavage step should be introduced to the protocol of automated synthesis. This step should be added after each step of oxidation of the growing oligomer chain <i>via</i> the Staudinger reaction. It was shown that the yield of the P–NH₂ oligonucleotide was almost entirely independent of the type of the dinucleotide fragment being modified, as well as of the localization of the P–NH₂ linkage in the chain. The attenuation of the destabilizing effect of the introduction of a single P–NH₂ linkage with decreasing ionic strength of the solution provided additional evidence for the electroneutral state of the inserted phosphoramidate linkage. <b>Conclusions:</b> A new approach to the automated synthesis of partially modified oligonucleotide derivatives bearing uncharged <i>N</i>-unsubstituted phosphoramidate linkages isostructural to native P–O linkages by an optimized solid-phase phosphoramidite protocol using the Staudinger reaction has been proposed.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2455 - 2472"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convenient Synthesis, Antibacterial Activity, and In Silico Studies of Novel 6-Phenoxy-4,5-dihydro-1,2,6-oxazaphosphinine 6-Oxides","authors":"A. Wahbi,&nbsp;M. A. Dridi,&nbsp;I. Dridi,&nbsp;H. Alimi,&nbsp;S. Touil","doi":"10.1134/S1068162024060074","DOIUrl":"10.1134/S1068162024060074","url":null,"abstract":"<p><b>Objective:</b> The main objective of this work was to develop a convenient synthesis of a new class of oxazaphosphorines, namely 6-phenoxy-4,5-dihydro-1,2,6-oxazaphosphinine 6-oxides (<b>IVa–IVe</b>), for antibacterial screening. <b>Methods:</b> Oxazaphosphorines (<b>IVa–IVe</b>) were obtained through a three-step approach involving the microwave-assisted conjugative addition of diphenyl phosphite to α,β-unsaturated ketones, followed by oximation and intramolecular cyclization. The newly synthesized oxazaphosphorines were screened for their <i>in vitro</i> antibacterial activity against Gram-positive (<i>Staphylococcus aureus</i>) and Gram-negative (<i>Escherichia coli</i>, <i>Salmonella typhimurium</i>, and<i> Pseudomonas aeruginosa</i>) bacteria. The obtained results were also correlated with the <i>in silico</i> molecular docking studies in DNA gyrase enzyme active site. <b>Results and Discussion:</b> Oxazaphosphorines (<b>IVa–IVe</b>) were obtained in 47–60% yields. The biological assays showed that these compounds exhibited appreciable antibacterial activity. Compound (<b>IVe</b>) was found to be the most potent antibacterial agent with an inhibition zone diameter of 9.66 ± 0.89 mm, and MIC and MBC values of 10 and 25 mg/mL respectively, when tested against <i>S. typhimurium</i>. We also observed a fairly good agreement between these experimental <i>in vitro</i> antibacterial outcomes and the <i>in silico</i> molecular docking results in DNA gyrase enzyme active site. <b>Conclusions:</b> We have successfully developed a convenient synthesis of a new class of oxazaphosphorines, namely 6-phenoxy-4,5-dihydro-1,2,6-oxazaphosphinine 6-oxides (<b>IVa–IVe</b>). When screened for their <i>in vitro</i> antibacterial activity, compound (<b>IVe</b>) was found to be the most potent antibacterial agent. We tried to correlate these results with those obtained in the <i>in silico</i> molecular docking study. The obtained results suggest that the synthesized compound (<b>IVe</b>) is a potential DNA gyrase inhibitor and could be used as a lead compound for developing new potent antibacterial drugs.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2134 - 2148"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Dipeptidylpeptidase-IV by (2S)-Cyanopyrrolidine Inhibitors of Prolyl Endopeptidase","authors":"G. I. Makarov,&nbsp;N. N. Zolotov,&nbsp;V. F. Pozdnev","doi":"10.1134/S1068162024060281","DOIUrl":"10.1134/S1068162024060281","url":null,"abstract":"<p><b>Objective:</b> Prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DPP4) are serine peptidases, cleaving peptides at the carboxyl group of proline residues. These enzymes are involved in the regulation of many physiological processes, participating in the production, modification, and utilization of neuropeptides and peptide hormones. We found that compounds of the X-Y-2-S-cyanopyrrolidine general formula, where X is a protecting group and Y is any amino acid other than glycine and proline, which are PEP inhibitors, also inhibit DPP4. To explain the unexpected ability of these compounds to inhibit DPP4, we set out to develop a structurally reasoned insights of their interaction with the PEP and DPP4 active sites. <b>Methods:</b> To achieve this goal, we synthesized a series of N-protected amino acid derivatives of 2-S-cyanopyrrolidine, determined their inhibition constants for PEP and DPP4, and performed molecular dynamics modeling of the structures of these complexes. <b>Results and Discussion:</b> X-Y-2-S-pyrrolidine PEP inhibitors can inhibit DPP4, if X is a benzyloxycarbonyl or succinyl protecting group and Y is not a glycine or proline residue, i.e., they are L-amino acid residues with side chains. Among them, <i>N</i>-benzyloxycarbonylamino-<i>L</i>-methionyl-2<i>S</i>-pyrrolidine-2-carbonitrile has pronounced antiamnesic activity. Molecular dynamics modeling showed that the large hydrophobic side chain of methionine or tryptophan residues in the inhibitor ensures its binding to the active site of DPP4, compensating for steric hindrance created by the N-protecting group. <b>Conclusions:</b> Using molecular dynamics modeling methods, we established a relationship between the structure of 2-<i>S</i>-cyanopyrrolidine amino acid derivatives and their ability to inhibit DPP4. This opens the prospect of creating new drugs, affecting the peptidergic link in the regulation of functional systems in normal conditions and in various pathological processes.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2366 - 2378"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Antisense Oligonucleotides, DNAzymes, and Their Bivalent Forms in RNAse H Dependent Cleavage of Folded RNA","authors":"M. V. Dubovichenko,&nbsp;V. Nnanyereugo,&nbsp;G. A. Bobkov,&nbsp;A. A. ElDeeb,&nbsp;D. M. Kolpashchikov","doi":"10.1134/S1068162024060219","DOIUrl":"10.1134/S1068162024060219","url":null,"abstract":"<p><b>Objective:</b> Antisense oligonucleotide (ASO) and DNAzyme (Dz) agents have been suggested for suppression specific mRNA <i>in vivo</i>. It was reported that Dz agents are more selective in recognition their targets than ASO. However, Dz failed to produce therapeutically significant drugs due to their low efficiency. Here we compared the performance of the two types of agents in cleavage a folded RNA fragment in reconstituted system containing RNase H. <b>Methods:</b> Thermodynamic parameters and predicted 2D-structure of the RNA fragments were obtained using RNAFold application in UNAFold web server. To perform the experiments with RNA cleavage by enzymes we used commercial Mg₂⁺-containing reaction 10X RNAse H Buffer (200 mM Tris-HCl (pH 8.3), 150 mM DTT, 1 M KCl, 45 mM MgCl₂). Results of RNA cleavage were visualized with 20% denaturing PAGE (AA : BA (29 : 1), 7 M Urea, 1× TBE) running 150 min at 80 V. <b>Results and Discussion:</b> Individual ASO agents were ~3­–6 times more active in RNA cleaving than the equivalent Dz agents. Both agents demonstrated low selectivity toward RNA cleavage. Combining two Dz complementary to the abutting position of the RNA target bivalent (BDD) agent improved RNA cleavage to the level of the most active ASO agent. <b>Conclusions:</b> Comparing the obtained data with published earlier for RNase H—free system suggests that RNase H stabilizes the Dz:RNA complex and reduces its selectivity but significantly increase RNA cleavage efficiency. The contribution of RNase H effects on the performance of Dz agents in cell culture and <i>in vivo</i> should be taken in account.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2558 - 2566"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Evaluation of NH2 and SH Linker Free Benzothiazole-Triazole Compounds: Insights into Antimicrobial Efficacy","authors":"Aamir R. Shama,&nbsp;Mehulkumar L. Savaliya,&nbsp;Snehal Lokhandwala","doi":"10.1134/S1068162024060141","DOIUrl":"10.1134/S1068162024060141","url":null,"abstract":"<p><b>Objective:</b> To evaluate the antimicrobial effectiveness of a novel 5-(1,3-benzothiazol-2-yl)-4-[(<i>E</i>)-(phenylmethylidene)amino]-4<i>H</i>-1,2,4-triazole-3-thiol derivatives. <b>Methods:</b> Starting from 2-aminothiophenol, a series of novel benzothiazole tethered triazole compounds were synthesized using conventional multi-step reactions. The reaction conditions were optimized for yield. Characterization was performed using ¹H, ¹³C NMR, IR, and mass spectrometry. To determine the antimicrobial activity, both the agar well diffusion method and micro broth dilution method were employed. Molecular docking was conducted with AutoDock Vina, and ADME analysis was performed using SwissADME. The evaluation of toxicity was carried out using ADMETlab 2.0. <b>Results and Discussion:</b> Compound with a 2-NO₂ substitution showed potent antibacterial activity against <i>E. coli</i>, with an inhibition of 50 µg/mL, similar to the standard drug chloramphenicol. The derivatives containing 3-Br and thiophene substitutions exhibited excellent activity against <i>P. aeruginosa</i>, with an inhibition concentration of 50 µg/mL. Moreover, the compounds with substitutions of 4-Br, 2,4-F, 4-F, and thiophene showed notable antifungal activity against <i>C. albicans</i> at a concentration of 250 µg/mL, surpassing the effectiveness of the standard drug griseofulvin. The results of molecular docking indicated that the compounds possessing 2-NO₂, 3-Br, and 2,4-F substitutions displayed the most potent binding affinities towards their target proteins. The ADMET properties of these compounds were thoroughly evaluated and confirmed their drug-like characteristics and pharmacokinetic viability. <b>Conclusions:</b> The results of the antimicrobial activity assays and molecular docking studies indicate that several of the synthesized compounds demonstrated potency equal to or exceeding that of standard drugs. Furthermore, the ADMET profiles of these compounds were favourable, suggesting good pharmacokinetic properties. These findings highlight the potential of the synthesized compounds as effective antimicrobial agents, warranting further investigation and development.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2344 - 2365"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, In Silico Studies, and Anticancer Activity of Novel Nitrobenzene Thiazolyl Hydrazones against the EGFR","authors":"Sonali S. Shinde,&nbsp;Jaydeo T. Kilbile,&nbsp;Shankar Thapa,&nbsp;Mahalakshmi S. Biradar,&nbsp;Sachin S. Bhusari,&nbsp;Pravin S. Wakte","doi":"10.1134/S1068162024060190","DOIUrl":"10.1134/S1068162024060190","url":null,"abstract":"<p><b>Objective:</b> Design, synthesis, characterization, and<i> in silico</i> studies of novel nitrobenzene thiazolyl hydrazones (<b>VIa–VIh</b>) and inhibitory action against the EGFR. <b>Methods:</b> All synthesized compounds were evaluated for their anticancer activity against selected cancer cell lines <i>in vitro</i> utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and EGFR enzymatic assay. Target molecule features were investigated through a computational study that included drug-likeness, ADMET profiling, and molecular docking. <b>Results and Discussion:</b> The compounds (<b>IVb</b>), (<b>IVe</b>), and (<b>IVh</b>) showed prominent anticancer activity with an IC₅₀ value of 15.45, 18.23, 10.69 μM, and 12.75, 16.05, 11.95 μM against chosen cancer cell lines A549, and MCF-7 respectively. Additionally, <i>in vitro</i> EGFR enzymatic activity provided insight into the process of anticancer action of the majority of the active molecules. According to a molecular docking study, every molecule binds to EGFR (PDB ID: 5D41) with high affinities. <b>Conclusions:</b> Among all, derivatives (<b>IVb</b>), (<b>IVe</b>), and (<b>IVh</b>) showed moderate inhibition compared to different tested derivatives. Thus, the present study of all novel nitrobenzene thiazolyl hydrazones could be further optimized to develop new EGFR inhibitors.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2483 - 2498"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Improvement Effects of Polymer-Based Microencapsulated Celecoxib in a Rat Model of Alzheimer’s Disease","authors":"Rajendra Herur Vishnumurthy,&nbsp;M. Gnana Ruba Priya,&nbsp;Prashant Tiwari,&nbsp;Viswas Raja Solomon","doi":"10.1134/S1068162024060189","DOIUrl":"10.1134/S1068162024060189","url":null,"abstract":"<p><b>Objective:</b> The microencapsulation of Celecoxib (CXB) using different polymers aimed to enhance its solubility and permeability profile for potential neuroprotective applications in neurodegenerative diseases like Alzheimer’s disease. <b>Methods:</b> The solvent evaporation method was used for microencapsulation of CXB formulation. Characterization and evaluation of microencapsulation was done by FT-IR, DSC, XRD, SEM, and dissolution methods. Neuroprotective effect was evaluated by Scopolamine induced rat model. <b>Results and Discussion:</b> The solvent evaporation method yielded microencapsulated CXB formulations with high drug loading and improved dissolution profiles. Scanning electron microscopy revealed morphological changes, while differential scanning calorimetry and X-ray diffraction confirmed the conversion of CXB to an amorphous state post-encapsulation. Fourier-transform infrared spectroscopy indicated the formation of hydrogen bonds between CXB and polymers. In behavioral studies, microencapsulated CXB demonstrated superior efficacy in mitigating cognitive impairment induced by scopolamine, suggesting its potential as a neuroprotective agent. This effect may be attributed to the activation of cholinergic pathways. <b>Conclusions:</b> Thus, microencapsulation presents a promising strategy to enhance the therapeutic efficacy of CXB for neurodegenerative disorders.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2312 - 2324"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Profile of Transgenic Birch Plants with the Conifer Cytosolic Glutamine Synthetase Gene GS1","authors":"V. G. Lebedev","doi":"10.1134/S1068162024060207","DOIUrl":"10.1134/S1068162024060207","url":null,"abstract":"<p>ve: Increasing tree productivity by genetic engineering methods is one of the main trends of forest biotechnology. A promising strategy for this is to improve the use efficiency of nitrogen, which is the main limiting factor of plant growth. For this purpose, the <i>GS1</i> gene from Scots pine was transferred to downy birch (<i>Betula pubescens</i>) plants. This gene encodes the cytosolic form of glutamine synthetase, the main enzyme of nitrogen metabolism in plants. Methods: To assess the effects of insertion of this gene, the birch plant metabolome was analyzed using GC-MS and HPLC-MS. Results and Discussion: GC-MS analysis found 197 metabolites in birch extracts, but the metabolomes of two transgenic clones showed no statistically significant differences from the control. Using the S-plot based on the OPLS-DA model, 32 metabolite markers affecting the separation of control and transgenic birch plants were detected; 22 of them were identified. Three metabolites among them were nitrogen-containing, including γ-aminobutyric acid, the immediate precursor of which is glutamine. HPLC-MS analysis found 48 metabolites, but transgenic plants did not differ from the control. GC-MS, however, showed a decrease in the content of two phenolic compounds in transgenic plants, which is characteristic of improved nitrogen supply. Conclusions: The study shows that modification of nitrogen metabolism in birch plants does not significantly affect the biochemical composition of tree shoots.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2596 - 2610"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Estrogen Receptors in the Therapeutic Effect of Oxyresveratrol, Phytoestrogen, During, and After Oxidative Stress","authors":"Cansu Kara Oztabag,&nbsp;Akif Hakan Kurt,&nbsp;Lokman Ayaz,&nbsp;Mehmet Ali Sungur","doi":"10.1134/S1068162024060037","DOIUrl":"10.1134/S1068162024060037","url":null,"abstract":"<p><b>Objective:</b> Oxidative stress plays a significant role in the development and progression of various neurodegenerative disorders, including aging, atherosclerosis, cancer, ischemia reperfusion, inflammation, rheumatoid arthritis, liver diseases. Additionally, it is implicated in retinal diseases (RD) such as glaucoma, diabetic retinopathy (DR), retinal vein occlusion (RVO), and age-related macular degeneration (AMD). In our study, we studied the therapeutic effect of oxyresveratrol, against H₂O₂-induced oxidative damage. Additionally, we investigated the role of estrogen receptors in the observed effects. <b>Methods:</b> Oxidative stress was induced by H₂O₂ in ARPE-19 cells. Oxyresveratrol was applied at seven different concentrations during and after oxidative stress. Besides, estrogen receptor inhibitors were applied 1 h before the treatment to investigate the role of estrogen receptors. Changes in cell viability were assessed using XTT. To investigate the effectiveness of oxyresveratrol at the molecular level, cell death detection, Caspase-3, and TOS measurement kits were employed. <b>Results and Discussion:</b> Our findings indicated that oxyresveratrol at concentrations of 10 and 100 µM reduced cell damage in ARPE-19 cells during and after-induced oxidative stress. Additionally, the therapeutic effect of oxyresveratrol in ARPE-19 cells during oxidative stress formation appeared to be dependent on estrogen receptors α and β, while the therapeutic effect after oxidative stress seemed to be GPER1-dependent. Furthermore, oxyresveratrol suppressed apoptosis in ARPE-19 cells under oxidative stress, reducing cell death, and both during and after oxidative stress, oxyresveratrol application decreased TOS levels. Although the antioxidant, anti-inflammatory, and neuroprotective effects of oxyresveratrol are well known, this is the first study to investigate its therapeutic effects on H₂O₂ induced oxidative stress in ARPE-19 cells and the involvement of estrogen receptors in these effects. <b>Conclusions:</b> We believe that oxyresveratrol may be an alternative therapy in the prevention and treatment of retinal diseases.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2445 - 2454"},"PeriodicalIF":1.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}