Current medicinal chemistry最新文献

{"title":"Anticancer Drug Discovery from Natural Compounds Targeting PI3K/AKT/mTOR Signaling Pathway.","authors":"Manuele Figueiredo da Silva, Arestides Alves Lins, Midiane Correia Gomes, Washley Phyama de Jesus Marinho, Rodrigo Santos Aquino de Araújo, Ricardo Olimpio de Moura, Peng Zhan, Igor José Dos Santos Nascimento, Edeildo Ferreira da Silva-Júnior","doi":"10.2174/0109298673325229240928040758","DOIUrl":"https://doi.org/10.2174/0109298673325229240928040758","url":null,"abstract":"<p><p>The term cancer is used to describe a complex pathology characterized by the uncontrollable proliferation of cells, which displays a fast metastatic spread, being a disease with difficult treatment. In this context, Phosphatidylinositol 3-kinase (PI3K) represents a promising pathway to be inhibited, aiming to develop anticancer agents, since it performs a pivotal role in regulating essential cellular processes, including cell proliferation, growth, autophagy, and apoptosis. In parallel, natural compounds can effectively represent a therapeutic strategy to fight against malignant cells. Then, compounds derived from various plant sources, such as flavonoids, terpenoids, alkaloids, coumarins, and lignans, have exhibited remarkable in vitro and in vivo anticancer properties. This review focused in the exploration of natural products targeting the PI3K/AKT/m-TOR signaling pathway, demonstrating that these compounds could even further investigated to reveal novel and effective anticancer drugs in the future.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399685","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":"Multi-Target Mechanisms of Si-Ni-San on Anxious Insomnia: An Example of Network-pharmacology and Molecular Docking Analysis.","authors":"Chih Ting Lin, Hsin Yi Lin, Wen Huang Peng, Lung Yuan Wu","doi":"10.2174/0109298673299665240924090617","DOIUrl":"https://doi.org/10.2174/0109298673299665240924090617","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Based on comprehensive network-pharmacology and molecular docking analysis, this study was intended to unveil the multiple mechanisms of Si-Ni-San (SNS) in treating anxious insomnia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The compounds of SNS were meticulously analyzed, selected and standardized with references to their pharmacological attributes. The components included chaihu (Bupleurum chinense DC.), baishao (Paeonia lactiflora Pall.), zhishi (Citrus aurantium L.) and gancao (Glycyrrhiza uralensis Fisch. ex DC.). We used the Traditional Chinese Medicine System Pharmacology (TCMSP) Database, Traditional Chinese Medicines Integrated Database (TCMID), GeneCards database, therapeutic target database (TTD) and comparative toxicogenomic database (CTD) to construct the components-compounds-targets networks and used Cytoscape 3.9.1 software to visualize the outcome. Afterwards, the STRING database and Cytoscape 3.9.1 software were utilized to construct and visualize the protein-protein interaction (PPI) network analysis. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also conducted through the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The molecular docking program was carried out using AutoDock 4.2 software to understand interactions between target receptors and compound ligands selected for study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We thoroughly sorted and filtered 31 pharmacologically active compounds from SNS. Subsequently, several potential target genes were predicted, of which there were 59 target genes distinctly associated with anxious insomnia. The PPI analysis indicated that the core target proteins included AKT1, IL6, TNF, SLC6A4, MAOA and GABRA2. The results of our study indicated that SNS potentially remediates anxious insomnia by reducing inflammation, neurodegeneration, and cell apoptosis of neurons. In addition, GO and KEGG enrichment analysis results indicated that SNS could modulate multiple aspects of anxious insomnia through mechanisms related to pathways of neuroactive ligand-receptor interaction. These pathways include various kinds of synaptic transmission pathways, and anti-inflammatory activity associated with response pathways. When we compared the components-compounds-targets networks and the compounds-targets-synaptic pathways networks, the five active compounds, including beta-Sitosterol, Kaempferol, Tetramethoxyluteolin, Isorhamnetin and Shinpterocarpin, were selected to conduct molecular docking experiments. Eleven target proteins, (AKT1, SLC6A4, ADRB2, MAOA, ACHE, ESR1, CYP3A4, CHRNA7, GABRA2, HTR2A and NOS3), which also play significant roles in regulating serotonergic, cholinergic, dopaminergic and GABAergic systems in the PPI network, were selected to act as receptors in molecular docking trials. The results showed that docking pairs isorhamnetin-AKT1, isorhamnetin-SLC6A4, β-sito","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460079","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":"Role of Ferroptosis in ALD: Focusing on Hepcidin and Besides Hepcidin.","authors":"Leijie Chen, Hejun Zhou, Zongyong Cheng, Deliang Liu, Yuyong Tan","doi":"10.2174/0109298673317526240924050651","DOIUrl":"https://doi.org/10.2174/0109298673317526240924050651","url":null,"abstract":"<p><p>Ascending incidence and poor outcomes make Alcoholic Liver Disease (ALD) a considerable public health concern. This review concluded the iron metabolism under physiology conditions and alcohol disturbance (leading to ferroptosis in ALD) and summarized the novel treatment, diagnosis, and prognosis of ferroptosis for ALD. ALD is characterized by alcohol-induced chronic metabolism disorder, peroxidation damage, and dysfunction of the anti-oxidant system. Current animal experiments and clinical studies identified ferroptosis as a new form of regulated cell death involved in ALD. One strong evidence is that the key iron regulatory hormone, hepcidin, is downgraded in ALD through NF-κB/IL-6/STAT3, BMP/SMAD, and Jak/STAT3 pathways, which would impair iron hemostasis and induce ferroptosis in ALD. Also, imbalance metabolism and other pathological responses in ALD induce and regulate ferroptosis, which proves ferroptosis participates in the pathophysiology of ALD via oxidative stress, steatosis, and fibrosis. Inhibition of ferroptosis via regulating hepcidin expression and metabolism impairment may provide new therapies for ALD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460083","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":"Lipidomics in Periodontal Disease Research: A Systematic Review.","authors":"Carolina Silva, Francisco Peixoto, Isabel Dias, Rosário Domingues, Carlos Viegas","doi":"10.2174/0109298673323591240923051742","DOIUrl":"https://doi.org/10.2174/0109298673323591240923051742","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Periodontal disease is a highly prevalent oral pathology in the human population, which has a significant local and systemic impact. Currently, multi-omics analyses, including lipidomics, are fundamental to obtaining an in-depth molecular understanding of the individual. Lipidomics is dedicated to the study of lipid species and their interactions in various health contexts. This specific multi-omics analysis is important for understanding the alteration of metabolism and signaling in disease, identifying biochemical markers, and potential therapeutic targets. This study aimed to carry out a systematic review of the existing scientific literature on lipidomics in periodontal disease and thus determine which molecules have already been analyzed and their potential in this specific disease.</p><p><strong>Methods: </strong>This study followed the recommendations of the PRISMA 2020 methodology. The inclusion criteria used were articles published in indexed journals between 2000 and 2023, written in English, and establishing an exclusive relationship about lipidomics in human periodontal disease. The articles were searched in three different databases.</p><p><strong>Results: </strong>Considering the criteria defined, only six articles were selected and zed individually in detail. In four of the six studies, differences in the lipidome of individuals with periodontal disease were identified. Furthermore, phosphoethanolamine ceramide was found to have potential as a diagnostic biomarker. Finally, the therapeutic potential of a lipoxin A4 analogue was also identified.</p><p><strong>Conclusion: </strong>These results reinforce the need for future research in this area so that the consequences of this disease on the lipidome can be identified.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388778","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":"Unveiling the Power of Mitochondrial Fission and Fusion: A Five-Gene Signature for Personalized Prognosis in Gastric Cancer.","authors":"Bin Zhou, Ping Tie, Dongbing Li, You Lu, Yuanhua Liu","doi":"10.2174/0109298673339515240930053412","DOIUrl":"https://doi.org/10.2174/0109298673339515240930053412","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial fission and fusion play important roles in tumorigenesis, progression and therapy. Dysregulation of these processes may lead to tumor progression, and regulation of these processes may provide novel strategies for cancer therapy. The involvement of genes related to mitochondrial fission and fusion (MD) in gastric cancer (GC) remains poorly understood.</p><p><strong>Objective: </strong>The aim of this study was to establish an MD gene signature for GC patients and to investigate its association with prognosis, tumor microenvironment and treatment response in GC.</p><p><strong>Methods: </strong>We use the TCGA-GC database as the cohort, focusing specifically on genes associated with MD. We conducted identification and consistency clustering analysis of differentially expressed genes in MD, conducted MD gene mutation and copy number variation analysis, as well as correlation and functional enrichment analysis between MD gene cluster classification and immune infiltration. TCGA-GC and GSE15459 were used to construct training and validation cohorts for the model. We used various statistical methods, including Cox and Lasso regression, to develop the model. We validated the model using bulk transcriptome and single- cell transcriptome datasets (GSE13861, GSE26901, GSE66229, and GSE13450). We used GSEA enrichment, CIBERSORT algorithm, ESTIMATE, and TIDE to gain insight into the annotation of MD signature and the characterization of the tumor microenvironment. OncoPredict was used to analyze the relationship between the PRG signature and the drug sensitivity. We validated the expression of several key genes in MD signature on GC cell lines using quantitative real-time PCR (qRT-PCR).</p><p><strong>Results: </strong>These MDs-related subtypes exhibited different prognosis and immune filtration patterns. A five-gene signature, comprising AGT, HCFC1, KIFC3, NOX4, and RIN1, was developed. There was a clear distinction in overall survival between low- and high-risk patients. The analyses showed further confirmation of the independent prognostic value of the gene signature. There was a notable correlation between the MD signature, immune infiltration and drug susceptibility. The expression levels of AGT, HCFC1, KIFC3, NOX4 and RIN1 mRNA were all increased in these GC cells.</p><p><strong>Conclusion: </strong>The MD signature has the capacity to significantly contribute to the prediction of personalized outcomes and the advancement of novel therapeutic strategies tailored for GC patients.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388781","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 of a Mitochondrial Membrane Permeability Transition Prognosis System in Colon Adenocarcinoma: Risk Stratification and Therapeutic Target Identification.","authors":"Bomiao Zhang, Mingyu Xia, Shihui Zhao, Yien Li, Chenfeng Yu, Liqiang Song, Shaoke Wang, Binbin Cui","doi":"10.2174/0109298673335900240920070746","DOIUrl":"https://doi.org/10.2174/0109298673335900240920070746","url":null,"abstract":"<p><strong>Aims: </strong>Explore the role of mitochondrial membrane permeability transition (MPT) in colon adenocarcinoma (COAD).</p><p><strong>Background: </strong>Further exploration of risk stratification for COAD prognostic assessment has important clinical value. MPT-related pathways play a key role in the pathogenesis of many human diseases, including tumorigenesis. Its impact on COAD is still unknown.</p><p><strong>Objective: </strong>Bioinformatics analysis was conducted by analyzing the GEO database and TCGA database, and the bioinformatics results were verified by in vitro experiments.</p><p><strong>Method: </strong>Through the analysis of the transcriptome data of 1008 COAD samples in the GEO database and TCGA database, the differential expressions of MPT-related genes in COAD were explored, followed by molecular subtype analysis based on MPT characteristics by univariate Cox algorithm analysis and the consensus clustering algorithm. The gene signature associated with MPT molecular subtypes was further identified and the MPT scoring system was established by the LASSO-univariate Cox analysis algorithm. After evaluating the prognostic value of the MPT scoring system in COAD patients via nomogram establishment, the clinical value of the MPT scoring system was comprehensively analyzed through somatic mutation characteristics analysis, immunotherapy response analysis, immunoinfiltration analysis, and drug sensitivity analysis. CCK-8, WB, PCR, colony formation method, and Transwell method were used to verify the effect of the screened target on the proliferation and invasion of COAD cells.</p><p><strong>Result: </strong>We successfully established a scoring system related to MPT and validated the prognostic value of COAD patients. The potential clinical value of the MPT scoring system was also analyzed. VSIG4 was selected for further in vitro experiments to verify the effect of the screened targets on the proliferation and invasion ability of COAD cells.</p><p><strong>Conclusions: </strong>We established an MPT scoring system for effective risk stratification of COAD patients, demonstrating the impact of MPT on the development of COAD and its potential value as an intervention factor.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388768","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":"Liposomal Nanoformulation-encapsulated Paclitaxel for Reducing Chemotherapy Side Effects in Lung Cancer Treatments: Recent Advances and Future Outlooks.","authors":"Kave Mohammad-Jafari, Seyed Morteza Naghib, M R Mozafari","doi":"10.2174/0109298673308951240921121345","DOIUrl":"https://doi.org/10.2174/0109298673308951240921121345","url":null,"abstract":"<p><p>Paclitaxel is one notable chemotherapy drug that is used to treat a number of cancers, including lung cancer. Nevertheless, it has drawbacks such as toxicity, low solubility in water, and the emergence of multidrug resistance (MDR). This article reviews the use of liposomal formulations to improve paclitaxel administration and efficacy for lung cancer therapy. Paclitaxel's pharmacological characteristics can be improved by liposomes through increased solubility, extended circulation, passive tumor targeting through leaky vasculature, and decreased side effects. Recent developments in paclitaxel liposomal formulations, including as cationic liposomes, conventional liposomes, targeted liposomes with particular ligands, and liposome-loaded microorganisms, are outlined in this article. In comparison to free paclitaxel, these nanoformulations exhibit enhanced cytotoxicity, cellular uptake, apoptosis, tumor growth suppression, and anticancer effects in lung cancer cell lines and animal models. One efficient way to get around the drawbacks of paclitaxel is to alter its size, makeup, and surface characteristics. This will let the medication accumulate and penetrate tumors more easily, avoid multidrug resistance, and cause less systemic toxicity. The article explores clinical studies showcasing the safety and therapeutic efficacy of liposomal paclitaxel for individuals afflicted with lung cancer. In its entirety, the document provides an in-depth examination of the potential enhancement in paclitaxel's dispersion and anti-tumor impacts through the utilization of liposomal technology when addressing diverse manifestations of lung cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388779","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":"Design, Synthesis, Docking Studies, and Biological Activity of Novel Analogs of Cyclophosphamide as Potential Anticancer Agents.","authors":"Khodayar Gholivand, Soobieh Alemi Rostami, Marzie Sabaghian, Sanam Sadeghi-Mohammadi, Azam Babaei, Rahime Eshaghi Malekshah, Hossein Naderi-Manesh","doi":"10.2174/0109298673332921240920065129","DOIUrl":"https://doi.org/10.2174/0109298673332921240920065129","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to present the synthesis and characterization of four novel analogs of cyclophosphamide (2, 3, 4, 7) and their related precursors (1, 5, 6) and assess their anticancer activity against breast cancerous (MCF-7) and normal (HUVEC) cells.</p><p><strong>Method: </strong>Notably, 2-(bis(2-chloroethyl)amino)-1,3,2-diazaphospholidine 2-oxide ((2)) and 2-(bis(2-hydroxyethyl)amino)-1,3,2-diazaphospholidine 2-oxide ((7)) exhibited concentration- dependent cytotoxicity against the MCF-7 cell line, with IC50 values of 8.98 and 28.74 μM, respectively.</p><p><strong>Result: </strong>Annexin V/PI staining and ROS assays demonstrated reduced cell viability and mitochondrial dysfunction. in silico studies involving DFT-D optimization and Molegro virtual docking against B-DNA dodecamer and STAT3 receptors revealed enhanced interactions for certain compounds compared to cyclophosphamide.</p><p><strong>Conclusion: </strong>Importantly, the in silico and in vitro results corroborated each other, supporting the potential anticancer efficacy of these novel analogs.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388767","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":"Quassinoids as Promising Anti-cancer Agents.","authors":"Tripti Mishra, Saima, Bimal Krishna Banik","doi":"10.2174/0109298673313760240911160930","DOIUrl":"https://doi.org/10.2174/0109298673313760240911160930","url":null,"abstract":"<p><p>The use of current anticancer drugs is hampered by significant side effects and high costs. In the pursuit of safer, more effective, and affordable options, researchers have turned to nature as a valuable source of potential anticancer compounds. Quassinoids, a class of natural terpenoids, have garnered attention for their anticancer properties. This comprehensive review aims to shed light on natural quassinoids and their anticancer effects, offering valuable insights for researchers dedicated to the development of novel anticancer therapeutics.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388780","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":"Integrated Exploration of Pyranocoumarin Derivatives as Synergistic Inhibitors of Dual-target for Mpro and PLpro Proteins of SARS-CoV-2 through Molecular Docking, ADMET Analysis, and Molecular Dynamics Simulation.","authors":"Imane Yamari, Lamiae El Bouamri, Oussama Abchir, Mohammed Bouachrine, Mhammed El Kouali, Abdelouahid Samadi, Samir Chtita","doi":"10.2174/0109298673331781240829094334","DOIUrl":"https://doi.org/10.2174/0109298673331781240829094334","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to explore the potential of natural anticoagulant compounds as synergistic inhibitors of the main protease (Mpro) and papain-like protease (PLpro) of SARS-CoV-2 and find effective therapies against SARS-CoV-2 by investigating the inhibitory effects of natural anticoagulant compounds on key viral proteases.</p><p><strong>Objective: </strong>The objectives of this study were to conduct rigorous virtual screening and molecular docking analyses to evaluate the binding affinities and interactions of selected anticoagulant compounds with Mpro and PLpro, to assess the pharmacokinetic and pharmacodynamic profiles of the compounds to determine their viability for therapeutic use, and to employ molecular dynamics simulations to understand the stability of the identified compounds over time.</p><p><strong>Methods: </strong>In this study, a curated collection of natural anticoagulant compounds was conducted. Virtual screening and molecular docking analyses were performed to assess binding affinities and interactions with Mpro and PLpro. Furthermore, pharmacokinetic and pharmacodynamic analyses were carried out to evaluate absorption, distribution, metabolism, and excretion profiles. Molecular dynamics simulations were performed to elucidate compound stability.</p><p><strong>Results: </strong>Natural compounds exhibiting significant inhibitory activity against Mpro and PLpro were identified. A dual-target approach was established as a promising strategy for attenuating viral replication and addressing coagulopathic complications associated with SARS-CoV-2 infection.</p><p><strong>Conclusion: </strong>The study lays a solid foundation for experimental validation and optimization of identified compounds, potentially leading to the development of precise treatments for SARS-CoV-2.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371234","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}