Current medicinal chemistry最新文献

{"title":"Molecular Docking in Drug Discovery: Techniques, Applications, and Advancements.","authors":"Cinthia Aguiar, Ihosvany Camps","doi":"10.2174/0109298673325827240926081845","DOIUrl":"https://doi.org/10.2174/0109298673325827240926081845","url":null,"abstract":"<p><p>The primary objective of this study is to conduct a comprehensive review of the significance of molecular docking in the field of drug discovery. This includes an examination of the various approaches and methods used in molecular docking, as well as an exploration of the techniques used for interpreting and validating docking results. To gather relevant data, a systematic search was conducted using Web of Science, PubMed, and Google Scholar. The search focused on articles related to molecular docking methodologies and their applications in drug discovery. Additionally, alternative techniques that can be used for more precise simulations of ligand-protein interactions were also considered. Molecular docking has proven to be an incredibly rich and valuable process in the field of drug discovery. Its flexibility allows for the incorporation of advanced computational techniques, thereby enhancing the reliability and efficiency of drug discovery processes. The results of the study highlights the significant strides made in the field of molecular docking, demonstrating its potential to revolutionize drug discovery. Molecular docking continues to evolve, with new advancements being made regularly. Despite the challenges faced, these advancements have significantly contributed to the enhancement of molecular docking, solidifying its position as a crucial tool in the field of drug discovery.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Booming Artificial Intelligence in Oral Cancer Diagnosis: From Image Processing to Stage Classification.","authors":"Shankari Gopalakrishnan, Dhamodharan Prabhu, Subash C B Gopinath","doi":"10.2174/0109298673340864241004052149","DOIUrl":"https://doi.org/10.2174/0109298673340864241004052149","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Obesity, Menopause, and Depression in Women's Health: An Attempt to Decipher the Complex Relationship.","authors":"Pervej Alom Barbhuiya, Manash Pratim Pathak","doi":"10.2174/0109298673317600240930052201","DOIUrl":"https://doi.org/10.2174/0109298673317600240930052201","url":null,"abstract":"<p><strong>Background: </strong>Menopause symptoms may be distressing, especially when they appear at a time when women are expected to play significant responsibilities in society. Numerous biological systems are influenced by the hormonal changes that start during the menopausal transition. This review attempts to decipher the complex relationship between obesity, menopause, and depression, citing some recent longitudinal and cross-sectional studies. Additionally, this study provides a summary of the different phytoestrogens, their sources, and probable mechanisms of action in addition to available therapeutic alternatives.</p><p><strong>Methodology: </strong>For this review purpose, the authors have gone through a vast number of articles from various scientific databases like PubMed, Google Scholar, and Web of Science.</p><p><strong>Results: </strong>It is becoming clear that the physiological basis for these menopausal symptoms is complicated and connected to estrogen deficiency, but not alone. Other hormones like FSH, LH, progesterone, and inhibin B are the major ones that are both directly and indirectly responsible for most of the menopausal symptoms. Numerous longitudinal and cross-sectional studies have found a direct relationship between the incidence of menopause and depression as well as obesity. Phytoestrogens like stilbene, lignans, isoflavone, and coumestan have been reported to be the alternatives to synthetic estrogen with lesser side effects, as reported in various studies.</p><p><strong>Conclusion: </strong>The complex relationship between depression, menopause, and obesity presents a complex obstacle to women's health and overall well-being. There might be a lot of promising prospects for revolutionary advancements in women's health during the menopausal stage in the future. Promising drug development that targets not just one but also the three conditions -obesity, menopause, and depression - as well as more thorough research are needed to improve the healthcare system for women who suffer from these conditions.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Cholesterol-related Gene Signature for Prognostic Assessment in Head and Neck Squamous Cell Carcinoma.","authors":"Jiarong Zheng, Dalong Shu, Rongwei Xu, Yucheng Zheng, Pei Lin, Yunfan Lin, Xinyuan Zhao, Li Cui, Xin Liao, Bing Guo","doi":"10.2174/0109298673336147241010065340","DOIUrl":"https://doi.org/10.2174/0109298673336147241010065340","url":null,"abstract":"<p><strong>Aim: </strong>This study seeks to develop a prognostic risk signature for head and neck squamous cell carcinoma (HNSCC) based on cholesterol-related genes (CholRG), aiming to enhance prognostic accuracy in clinical practice.</p><p><strong>Background: </strong>HNSCC poses significant challenges due to its aggressive behavior and limited response to standard treatments, resulting in elevated morbidity and mortality rates.In order to improve prognostic prediction in HNSCC, our study is inspired by the realization that cholesterol metabolism plays a critical role in accelerating the progression of cancer. To this end, we are developing a unique risk signature using CholRG.</p><p><strong>Objective: </strong>The aim of this study was to create a CholRG-based risk signature to predict HNSCC prognosis, aiding in clinical decision-making accurately.</p><p><strong>Method: </strong>The TCGA HNSCC dataset, along with GSE41613 and GSE65858, was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. A CholRG-based risk signature was then developed and validated across various independent HNSCC cohorts. Moreover, a nomogram model incorporating CholRG-based risk signature was established. Additionally, functional enrichment analysis was conducted, and the immune landscapes of the high- and low-risk groups were compared. Finally, in vitro experiments were performed using lipid-based transfection to deliver siRNAs targeting ACAT1 to SCC1 and SCC23 cell lines, further examining the effects of ACAT1 knockdown on these cells.</p><p><strong>Results: </strong>Utilizing RNA-seq, microarray, and clinical data from public databases, we constructed and validated a CholRG-based risk signature that includes key genes such as ACAT1, CYP19A1, CYP27A1, FAXDC2, INSIG2, PRKAA2, and SEC14L2, which can effectively predict the clinical outcome of HNSCC. Additionally, our findings were reinforced by a nomogram model that integrates the risk score with clinical variables for more clinically practical prognostic assessment. In addition, patients at high risk show hypoxia and increased oncogenic pathways such as mTORC1 signaling, as well as a suppressed immune microenvironment marked by a reduction in the infiltration of important immune cells. Notably, in vitro experiments showed that ACAT1 depletion significantly suppressed the proliferation, colony formation, and invasion capabilities of HNSCC cells, confirming ACAT1's role in promoting malignancy.</p><p><strong>Conclusion: </strong>Collectively, our study not only underscores the importance of cholesterol metabolism in HNSCC pathogenesis but also highlights the CholRG-based risk signature as a promising tool for enhancing prognostic accuracy and personalizing therapeutic strategies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin Is a Novel Candidate for Glioblastoma Treatment? A Review.","authors":"Arian Rezaee, Mehrsa Radmanesh, Atena Asghari, Ahmad Nazari, Amir Abbas Shahidi, Amir Modarresi Chahardehi, Reza Arefnezhad, Tahreh Farkhondeh, Mohammad Saminin, Saeed Samarghandian","doi":"10.2174/0109298673311502240930043117","DOIUrl":"https://doi.org/10.2174/0109298673311502240930043117","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a malignant primary brain tumor with a poor prognosis and high recurrence rates. At present, the current treatments available for GBM patients can only prolong their overall survival and cannot provide a complete cure. Discovering an effective therapy against the disease is a challenge due to its recurrence and resistance to common available treatments for GBM. Several natural products have been documented to possess the potential to function as anticancer agents through diverse mechanisms. Astaxanthin (AXT) is an orange-red pigment that is a natural lipophilic and xanthophyll carotenoid derived mostly from microalgae. Numerous studies have examined that AXT impacts GBM cells in laboratory settings and animal models. This review aims to provide the latest information about the potential of astaxanthin as a novel therapeutic option for GBM. AXT has been targeted more on reactive oxygen species (ROS), and suppressed tumor growth in vitro and in vivo conditions. The available data suggests that AXT might serve as a key component in the development of innovative cancer therapies, especially for glioblastoma.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of 2,4-Bis(trifluoromethyl)benzaldehyde Hybrid Thiosemicarbazones as Prolyl Oligopeptidase Inhibitors for Neurodegenerative Disorders and their In-silico Analysis.","authors":"Anam Rubbab Pasha, Saeed Ullah, Sobia Ahsan Halim, Ajmal Khan, Javid Hussain, El-Kott Attalla F, Muhammad Moazzam Naseer, Waleed Eltantawy, Ahmed Al-Harrasi, Zahid Shafiq","doi":"10.2174/0109298673325023240909101327","DOIUrl":"https://doi.org/10.2174/0109298673325023240909101327","url":null,"abstract":"<p><strong>Introduction: </strong>Prolyl-specific oligopeptidase (POP), one of the brain's highly expressed enzymes, is an important target for the therapy of central nervous system disorders, notably autism spectrum disorder, schizophrenia, Parkinson's, Alzheimer's disease, and dementia.</p><p><strong>Method: </strong>The current study was designed to investigate 2,4-bis(trifluoromethyl) benzaldehyde- based thiosemicarbazones as POP inhibitors to treat the above-mentioned disorders. A variety of techniques, such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and Fourier-transform infrared spectroscopy (FTIR), were used for the structural confirmation of synthesized compounds. After in-vitro evaluation, all of these compounds were found to be prominent inhibitors of the POP enzyme (IC50= 10.14 - 41.73 μM).</p><p><strong>Result: </strong>Compound 3a emerged as the most active compound (IC50 10.14 ± 0.72 μM) of the series. The kinetic study of the most active 3a (Ki =13.66 0.0012 μM) indicated competitive inhibition of the aforementioned enzyme.</p><p><strong>Conclusion: </strong>Moreover, molecular docking depicted a noticeable role of thiosemicarbazide moiety in the binding of these molecules within the active site of the POP enzyme.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Novel Indolyl Aryl Sulfone-clubbed Hydrazone Derivatives as Potential HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Molecular Modeling and QSAR Studies.","authors":"Hazrat Ali, Abdul Latif, Mumtaz Ali, Ammara, Muhammad Waqas, Manzoor Ahmad, Asaad Khalid, Ajmal Khan, Ahmed Al-Harrasi","doi":"10.2174/0109298673318987240926052450","DOIUrl":"https://doi.org/10.2174/0109298673318987240926052450","url":null,"abstract":"<p><strong>Background: </strong>Non-Nucleoside Reverse Transcriptases Inhibitors (NNRTIs) are among the most extensively studied enzymes for understanding the biology of Human Immunodeficiency Viruses (HIV) and designing inhibitors for managing HIV infections. Indolyl aryl sulfones (IASs), an underexplored class of potent NNRTIs, require further exploration for the development of newer drugs for HIV.</p><p><strong>Aims: </strong>In this context, we synthesized a series of novels by Indolyl Aryl Sulfones with a hydrazone moiety at the carboxylate site of the indole nucleus. A 2D-QSAR model was developed to predict Reverse Transcriptase inhibitory activity against wild-type RT (WT-RT) enzyme.</p><p><strong>Method: </strong>The model was successfully applied to predict the HIV-1 inhibitory activity of known Indolyl Aryl Sulfones. Considering the reliability, robustness, and reproducibility of the 2D-QSAR model, we made an in-silico prediction of the RT inhibition for our synthesized compounds (1-14).</p><p><strong>Results: </strong>Molecular docking and dynamics simulations established our synthesized Indolyl Aryl Sulfones, particularly compounds 23, 24, and 28, as effective NNRTIs by stabilizing HIV reverse transcriptase's structure. Binding energy calculations revealed compound 28 as the strongest inhibitor (-43.21 ± 0.09 kcal/mol), followed by 23 (-40.94 ± 0.10 kcal/mol) and 24 (-39.18±0.08 kcal/mol), emphasizing their binding affinity towards HIV reverse transcriptase.</p><p><strong>Conclusion: </strong>In summary, the synthesized Indolyl Aryl Sulfones, particularly compounds 23, 24, and 28, demonstrate significant potential as Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) against HIV. These results highlight the promising role of these compounds in developing novel NNRTIs for managing HIV infections.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, DFT, ADMET, and Docking studies of Novel Sulfonyl Piperidine Analogues containing 2,3-Dihydrobenzofuran-5-Carboxamide.","authors":"Tummuri Sudheer Reddy, Karreddula Raja, Gopi Krishna Pitchika, Manubolu Surya Surendra Babu","doi":"10.2174/0109298673329232241007101050","DOIUrl":"https://doi.org/10.2174/0109298673329232241007101050","url":null,"abstract":"<p><strong>Background: </strong>The development of effective anti-cancer medicines with low side effects is imperative as cancer continues to be a leading cause of death globally. By obstructing the survival and growth of cancer cells, small-molecule medications have made tremendous progress in the field of cancer research. Several bioactive heterocyclic compounds, including derivatives of piperidine and 2,3-dihydrobenzofuran, have shown great promise and are found in various anti-cancer medications. Cancer growth and metastasis are hindered by these small molecule inhibitors, which interfere with vital signals that drive cancer cell proliferation.</p><p><strong>Objective: </strong>This study focuses on the synthesis and evaluation of novel Sulfonyl Piperidine Analogues containing 2,3-Dihydrobenzofuran-5-Carboxamide as potential anti-- cancer agents.</p><p><strong>Methods: </strong>The synthesized compounds were characterized using spectroscopic techniques such as 1H NMR and ESI-MS. Protein-drug interaction studies, DFT analysis, and target prediction techniques were employed. The anti-cancer properties of the compounds were evaluated in vitro against MCF-7 cell lines. Compounds 5 and 7 were specifically investigated for their growth-inhibitory effects on MCF7 breast cancer cells.</p><p><strong>Results: </strong>Compounds5 and 7 demonstrated strong binding affinity towards both mutated BRCA1 (PDB ID: 1N5O) and BRCA2 (PDB ID:8BR9). Furthermore, they displayed notable efficacy against MCF-7 cell lines.</p><p><strong>Conclusion: </strong>Synthesized compounds displayed activity against MCF-7 cell lines, supporting findings from in-silico predictions. Further investigations are warranted to elucidate the mechanisms of action of these selected molecules against MCF-7 cell types.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Mechanism of RSV for the Treatment of COVID-19 and Idiopathic Pulmonary Fibrosis via Suppressing Inflammation Response Through IL-17 Signaling Pathway from the Perspectives of in silico Study.","authors":"Jiahao Wang, Jiamiao Shi, Ning Jia, Qinru Sun","doi":"10.2174/0109298673308841240930044555","DOIUrl":"https://doi.org/10.2174/0109298673308841240930044555","url":null,"abstract":"<p><strong>Background: </strong>Both coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) could cause severe pulmonary injury and have extremely dismal prognoses with a high risk of mortality. Resveratrol (RSV), a natural polyphenol, has promising potential in the treatment of viral infection and pulmonary fibrosis.</p><p><strong>Objective: </strong>The purpose of this research was to investigate the unclear mechanism of RSV as an anti-COVID-19 and IPF therapy.</p><p><strong>Method: </strong>Utilizing relevant databases, the intersection of genes related to IPF, COVID-19, and possible RSV targets was discovered. Then the obtained targets were investigated using GO and KEGG analysis, TP and PPI network analysis. Furthermore, the binding affinities between core targets and RSV were calculated using molecular docking.</p><p><strong>Results: </strong>The 1101 COVID-19 targets, 2166 IPF targets, and 341 RSV targets intersected with 21 overlapping targets. PPI network reveals the interactions among targets and TP network reveals interactions between targets and pathways. Five targets including JUN, CCL2, CXCL8, IL6, and SERPINE1 were identified as the core targets through two network analyses. GO analysis demonstrated chemotaxis, inflammatory response and angiogenesis were the significant pathophysiological processes. Combing TP network analysis and KEGG analysis, IL-17 signaling pathway was considered as the significant pathway. Except for JUN, molecular docking showed the binding energies of other four targets were lower than -5 kcal/mol indicating intimate interactions between RSV and other targets.</p><p><strong>Conclusions: </strong>Our research elucidate the targets, pathways and pathophysiological processes of RSV involved in effects of anti-COVID-19 and IPF, suggesting RSV could be a therapeutic candidate for reducing infection and fibrosis.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction Associated with mtDNA Mutation: Mitochondrial Genome Editing in Atherosclerosis Research.","authors":"Victoria A Khotina, Andrey Y Vinokurov, Vasily V Sinyov, Alexander D Zhuravlev, Daniil Y Popov, Vasily N Sukhorukov, Igor A Sobenin, Alexander N Orekhov","doi":"10.2174/0109298673323639240926095549","DOIUrl":"https://doi.org/10.2174/0109298673323639240926095549","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is a complex cardiovascular disease often associated with mitochondrial dysfunction, which can lead to various cellular and metabolic abnormalities. Within the mitochondrial genome, specific mutations have been implicated in contributing to mitochondrial dysfunction. Atherosclerosis-associated m.15059G>A mutation has been of particular interest due to its potential role in altering mitochondrial function and cellular health.</p><p><strong>Objective: </strong>This study aims to investigate the role of the atherosclerosis-associated m.15059G>A mutation in the development of mitochondrial dysfunction in monocyte-- like cells.</p><p><strong>Methods: </strong>Monocyte-like cytoplasmic hybrid cell line TC-HSMAM1, which contains the m.15059G>A mutation in mtDNA, was used. The MitoCas9 vector was utilized to eliminate mtDNA copies carrying the m.15059G>A mutation from TC-HSMAM1 cybrids. Mitochondrial membrane potential, generation of reactive oxygen species, and lipid peroxidation levels were assessed using flow cytometry. Cellular reduced glutathione levels were assessed using the confocal microscopy. The oxygen consumption rate was measured using polarographic oxygen respirometry.</p><p><strong>Results: </strong>The elimination of the m.15059G>A mutation resulted in a significant increase in mitochondrial membrane potential and improved mitochondrial efficiency while also causing a decrease in the generation of reactive oxygen species, lipid peroxidation, as well as cellular bioenergetic parameters, such as proton leak and non-mitochondrial oxygen consumption. At the same time, no changes were found in the intracellular antioxidant system after the mitochondrial genome editing.</p><p><strong>Conclusions: </strong>The presence of the m.15059G>A mutation contributes to mitochondrial dysfunction by reducing mitochondrial membrane potential, increasing the generation of reactive oxygen species and lipid peroxidation, and altering mitochondrial bioenergetics. Elimination of the mtDNA containing atherogenic mutation leads to an improvement in mitochondrial function.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}