Current computer-aided drug design最新文献

{"title":"Computational Analysis of <i>Bacopa monnieri</i> (L.) Wettst. Compounds for Drug Development against Neurodegenerative Disorders.","authors":"Satyam Sangeet,&nbsp;Arshad Khan,&nbsp;Saurov Mahanta,&nbsp;Nabamita Roy,&nbsp;Sanjib Kumar Das,&nbsp;Yugal Kishore Mohanta,&nbsp;Muthupandian Saravanan,&nbsp;Hui Tag,&nbsp;Pallabi Kalita Hui","doi":"10.2174/1573409918666221010103652","DOIUrl":"https://doi.org/10.2174/1573409918666221010103652","url":null,"abstract":"<p><strong>Aim: </strong>With several experimental studies establishing the role of Bacopa monnieri as an effective neurological medication, less focus has been employed to explore how effectively Bacopa monnieri brings about this property. The current work focuses on understanding the molecular interaction of the phytochemicals of the plant against different neurotrophic factors to explore their role and potential as potent anti-neurodegenerative drugs.</p><p><strong>Background: </strong>Neurotrophins play a crucial role in the development and regulation of neurons. Alterations in the functioning of these Neurotrophins lead to several Neurodegenerative Disorders. Albeit engineered medications are accessible for the treatment of Neurodegenerative Disorders, due to their numerous side effects, it becomes imperative to formulate and synthesize novel drug candidates.</p><p><strong>Objective: </strong>This study aims to investigate the potential of Bacopa monnieri phytochemicals as potent antineurodegenerative drugs by inspecting the interactions between Neurotrophins and target proteins.</p><p><strong>Methods: </strong>The current study employs molecular docking and molecular dynamic simulation studies to examine the molecular interactions of phytochemicals with respective Neurotrophins. Further inspection of the screened phytochemicals was performed to analyze the ADME-Tox properties in order to classify the screened phytochemicals as potent drug candidates.</p><p><strong>Results: </strong>The phytochemicals of Bacopa monnieri were subjected to in-silico docking with the respective Neurotrophins. Vitamin E, Benzene propanoic acid, 3,5-bis (1,1- dimethylethyl)- 4hydroxy-, methyl ester (BPA), Stigmasterol, and Nonacosane showed an excellent binding affinity with their respective Neurotrophins (BDNF, NT3, NT4, NGF). Moreover, the molecular dynamic simulation studies revealed that BPA and Stigmasterol show a very stable interaction with NT3 and NT4, respectively, suggesting their potential role as a drug candidate. Nonacosane exhibited a fluctuating binding behavior with NGF which can be accounted for by its long linear structure. ADME-Tox studies further confirmed the potency of these phytochemicals as BPA violated no factors and Vitamin E, Stigmasterol and Nonacosane violated 1 factor for Lipinski's rule. Moreover, their high human intestinal absorption and bioavailability score along with their classification as non-mutagen in the Ames test makes these compounds more reliable as potent antineurodegenerative drugs.</p><p><strong>Conclusion: </strong>Our study provides an in-silico approach toward understanding the anti-neurodegenerative property of Bacopa monnieri phytochemicals and establishes the role of four major phytochemicals which can be utilized as a replacement for synthetic drugs against several neurodegenerative disorders.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 1","pages":"24-36"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469970","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":"A Novel <i>in silico</i> SELEX Method to Screen and Identify Aptamers against <i>Vibrio cholerae</i>.","authors":"Hamid Reza Rasouli Jazi,&nbsp;Mehdi Zeinoddini,&nbsp;Seyed Shahriar Arab","doi":"10.2174/1573409919666230126101635","DOIUrl":"https://doi.org/10.2174/1573409919666230126101635","url":null,"abstract":"<p><strong>Background: </strong>Vibrio cholerae, the causative agent of cholera, has been responsible for global epidemics and many other problems over the centuries. It is one of the main public health issues in less-developed and developing countries and is considered one of the deadliest infectious agents. Therefore, precise and susceptible detection of V. cholerae</i> from environmental and biological samples is critical. Aptamers provide a rapid, sensitive, highly specific, and inexpensive alternative to traditional methods.</p><p><strong>Objective: </strong>The present study develops a new protocol inspired by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) to implement an in silico</i> aptamer selection against V. cholerae</i>, which can also be employed in the case of other pathogenic microorganisms.</p><p><strong>Methods: </strong>First, we built an oligonucleotide pool and screened it based on the secondary structure. Following that, we modeled the tertiary structures of filtered sequences and performed RNAprotein dockings to assess binding affinities between RNA sequences and Outer Membrane Protein U (OmpU), an effective marker in distinguishing epidemic strains of V. cholerae</i>, which constitute up to 60% of the total outer membrane protein. Finally, we used molecular dynamics simulation to validate the results.</p><p><strong>Results: </strong>Three sequences (ChOmpU^apta) were proposed as final aptameric candidates. Analysis of the top-ranked docking results revealed that these candidate aptamers bound to all subunits of OmpU at the extracellular side with high affinity. Moreover, ChOmpU^apta-3 and ChOmpU^apta-2 were fully stable and formed strong bonds under dynamic conditions.</p><p><strong>Conclusion: </strong>We propose incorporating these candidate sequences into aptasensors for V. cholerae</i> detection.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 6","pages":"416-424"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9475395","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":"The Determination of Molecular and Toxicological Mechanisms of Cucurbitacin E in Model Organism <i>Drosophila melanogaster</i> and Various Cancer Cell Lines: Molecular Modelling, Docking and Dynamic Simulation Studies.","authors":"Aydın Ş Tunçbilek,&nbsp;Serap Yalçın Azarkan,&nbsp;Fahriye Sümer Ercan","doi":"10.2174/1573409919666221031112223","DOIUrl":"https://doi.org/10.2174/1573409919666221031112223","url":null,"abstract":"<p><strong>Introduction: </strong>Cucurbitacins are one of the most important components of Ecballium elaterium. Among the cucurbitacins, Cucurbitacin E was the first to be isolated. This study focused on screening the anticancer and insecticidal potential of Cucurbitacin E by the in-vitro, invivo, and in-silico methods.</p><p><strong>Methods: </strong>In the study, toxicity analysis of Cucurbitacin E was determined on HeLa, Caco 2 cancer cell lines and D. melanogaster. While the expression levels of the BAD, BCL-2, AKT-1 and H-purine genes of cancer cell lines were determined, the CG15530, BUFFY, AKT-1 and Purine genes of D. melanogaster were determined by RT-PCR. Besides, molecular docking and dynamic properties of Cucurbitacin E with human and insectoid enzymes were presented in silico.</p><p><strong>Results: </strong>The IC₅₀ value of Cucurbitacin E in the HeLa ovarian and Caco 2 colon cancer cell lines was determined to be 42 ug/ml and 85 ug/ml, respectively. The LC₅₀ and LC₉₉ doses for fruit flies were determined to be 47,693 μg/ml and 133,251 μg/ml, respectively. Gene expression analysis revealed that Cucurbitacin E showed the greatest effect on Purine and AKT-1 genes in D. melanogaster. We analyzed all genes by Western blot but did not detect significant changes in genes other than H-purine. In silico studies revealed that the Purine protein of D. melanogaster had the highest bonding energy with Cucurbitacin E as a ligand. Similarly, Cucurbitacin E showed great affinity towards H-purine (-10.2 kcal/mol). Molecular dynamics simulation studies were also performed to determine the stability of the dynamic process.</p><p><strong>Conclusion: </strong>As a result of our in vivo, in vitro and bioinformatic analyzes, it has been seen that Cucurbitacin E is effective against the cancer types and model insects studied.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 2","pages":"81-93"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9818084","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":"Identification of Potential Inhibitors of PDE5 based on Structure-based Virtual Screening Approaches.","authors":"Lei Xu,&nbsp;Lilei Sun,&nbsp;Peng Su,&nbsp;Teng Ma,&nbsp;Yingcong Yu,&nbsp;Haibin Liu,&nbsp;Xianfeng Huang","doi":"10.2174/1573409919666221208143327","DOIUrl":"https://doi.org/10.2174/1573409919666221208143327","url":null,"abstract":"<p><strong>Background: </strong>Phosphodiesterase type 5 (PDE5), exclusively specific for cyclic guanidine monophosphate (cGMP), a potential target for the therapy of various diseases, and PDE5 inhibitors could be used as a treatment for erectile dysfunction (ED) or chronic pulmonary hypertension.</p><p><strong>Objective: </strong>In the present study, we carried out an integrated computer-aided virtual screening technique against the natural products in the ZINC database to discover potential inhibitors of PDE5.</p><p><strong>Methods: </strong>Pharmacophore, molecular docking and ADMET (Absorption, distribution, metabolism, excretion and toxicity) properties filtration were used to select the PDE5 inhibitors with the best binding affinities and drug-like properties. The binding modes of PDE5 inhibitors were investigated, and these complexes' stabilities were explored by molecular dynamic simulations and MM/GBSA free energy calculations.</p><p><strong>Results: </strong>Two natural compounds (Z171 and Z283) were identified and may be used as a critical starting point for the development of novel PDE5 inhibitors. The MM/GBSA free energy decomposition analysis quantitatively analyzed the importance of hydrophobic interaction in PDE5- ligands binding.</p><p><strong>Conclusion: </strong>In this study, we identified two novel natural compounds from the ZINC database to effectively inhibit PDE5 through virtual screening. The novel scaffolds of these compounds can be used as the starting templates in the drug design of PDE5 inhibitors with good pharmacokinetic profiles. These results may promote the de novo design of new compounds against PDE5.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 3","pages":"234-242"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9818117","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":"Computational Search for Potential COVID-19 Drugs from Ayurvedic Medicinal Plants to Identify Potential Inhibitors against SARS-CoV-2 Targets.","authors":"V Alagarsamy,&nbsp;V Raja Solomon,&nbsp;P Shyam Sundar,&nbsp;V S Kulkarni,&nbsp;M T Sulthana,&nbsp;A Dharshini Aishwarya,&nbsp;B Narendhar,&nbsp;S Murugesan","doi":"10.2174/1573409919666221117145404","DOIUrl":"https://doi.org/10.2174/1573409919666221117145404","url":null,"abstract":"<p><strong>Background: </strong>To date, very few small drug molecules are used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been discovered since the epidemic commenced in November 2019. SARS-CoV-2 RdRp and spike protein are essential targets for drug development amidst whole variants of coronaviruses.</p><p><strong>Objective: </strong>This study aims to discover and recognize the most effective and promising small molecules against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and spike protein targets through molecular docking screening of 39 phytochemicals from five different Ayurveda medicinal plants.</p><p><strong>Methods: </strong>The phytochemicals were downloaded from PubChem, and SARS-CoV-2 RdRp and spike protein were taken from the protein data bank. The molecular interactions, binding energy, and ADMET properties were analyzed.</p><p><strong>Results: </strong>Molecular docking analysis identified some phytochemicals, oleanolic acid, friedelin, serratagenic acid, uncinatone, clemaphenol A, sennosides B, trilobine and isotrilobine from ayurvedic medicinal plants possessing greater affinity against SARS-CoV-2-RdRp and spike protein targets. Two molecules, namely oleanolic acid and sennosides B, with low binding energies, were the most promising. Furthermore, based on the docking score, we carried out MD simulations for the oleanolic acid and sennosides B-protein complexes.</p><p><strong>Conclusion: </strong>Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike protein of SARS-CoV-2.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 1","pages":"51-67"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9118154","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":"Relevance of Machine Learning to Predict the Inhibitory Activity of Small Thiazole Chemicals on Estrogen Receptor.","authors":"Jayaprakash Venkatesan,&nbsp;Thangavelu Saravanan,&nbsp;Karuppaiyan Ravindran,&nbsp;Thangavelu Prabha,&nbsp;Selvaraj Jubie,&nbsp;Jayapalan Sudeepan,&nbsp;M V N L Chaitanya,&nbsp;Thangavel Sivakumar","doi":"10.2174/1573409919666221121141646","DOIUrl":"https://doi.org/10.2174/1573409919666221121141646","url":null,"abstract":"<p><strong>Background: </strong>Drug discovery requires the use of hybrid technologies for the discovery of new chemical substances. One of those interesting strategies is QSAR via applying an artificial intelligence system that effectively predicts how chemical alterations can impact biological activity via in-silico.</p><p><strong>Aim: </strong>Our present study aimed to work on a trending machine learning approach with a new opensource data analysis python script for the discovery of anticancer lead via building the QSAR model by using 53 compounds of thiazole derivatives.</p><p><strong>Methods: </strong>A python script has been executed with 53 small thiazole chemicals using Google collaboratory interface. A total of 82 CDK molecular descriptors were downloaded from \"chemdes\" web server and used for our study. After training the model, we checked the model performance via cross-validation of the external test set.</p><p><strong>Results: </strong>The generated QSAR model afforded the ordinary least squares (OLS) regression as R² = 0.542, F=8.773, and adjusted R² (Q2) =0.481, std. error = 0.061, reg.coef_ developed were of, - 0.00064 (PC1), -0.07753 (PC2), -0.09078 (PC3), -0.08986 (PC4), 0.05044 (PC5), and reg.intercept_ of 4.79279 developed through stats models, formula module. The performance of test set prediction was done by multiple linear regression, support vector machine, and partial least square regression classifiers of sklearn module, which generated the model score of 0.5424, 0.6422 and 0.6422 respectively.</p><p><strong>Conclusion: </strong>Hence, we conclude that the R2values (i.e. the model score) obtained using this script via three diverse algorithms were correlated well and there is not much difference between them and may be useful in the design of a similar group of thiazole derivatives as anticancer agents.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 1","pages":"37-50"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9118155","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":"<i>In silico</i> Prediction and Evaluation of Human Parainfluenza Virus-3 CD4⁺ T Cell Epitopes.","authors":"Peyman Bemani,&nbsp;Mozafar Mohammadi","doi":"10.2174/1573409919666221205122633","DOIUrl":"https://doi.org/10.2174/1573409919666221205122633","url":null,"abstract":"<p><strong>Background: </strong>Human parainfluenza viruses type 3 (HPIV-3) through bronchiolitis and pneumonia is a common cause of lower respiratory tract infections. It is the main cause of hospitalization of infants and young children and also one of the main causes of morbidity and mortality in immuno-compromised and transplant patients. Despite many efforts, there is currently no specific anti-HPIV-3 drug or approved vaccine to prevent and control the virus. Identification of HPIV-3 epitopes with the capability of binding to human leukocyte antigen (HLA) class II molecules can be helpful in designing new vaccine candidates against HPIV-3 infection, and also can be useful for the in vitro stimulation and proliferation of HPIV-3-specific T cells for transplant and immunocompromised patients.</p><p><strong>Objective: </strong>To predict and comprehensively evaluate CD4⁺T cell epitope (HLA-II binders) from four main HPIV-3 antigens.</p><p><strong>Methods: </strong>In the present work, we predicted and comprehensively evaluated CD4⁺T cell epitope (HLA-II binders) from four main HPIV-3 antigens, including fusion protein (F), hemagglutininneuraminidase (HN), nucleocapsid (N) and matrix (M) proteins using bio- and immunoinformatics software. The toxicity, allergenicity, Blast screening and population coverage of the predicted epitopes were evaluated. The binding ability of the final selected epitopes was evaluated via a docking study.</p><p><strong>Results: </strong>After several filtering steps, including blast screening, toxicity and allergenicity assay, population coverage and docking study, 9 epitopes were selected as candidate epitopes. The selected epitopes showed high population coverage and docking studies revealed a significantly higher binding affinity for the final epitopes in comparison with the negative control peptides.</p><p><strong>Conclusion: </strong>The final selected epitopes could be useful in designing vaccine candidates and for the treatment of immune-compromised individuals and patients with transplantation.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 3","pages":"163-175"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9457509","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":"Revisiting the South Indian Traditional Plants against Several Targets of SARS-CoV-2 - An <i>in silico</i> Approach.","authors":"Srikanth Jupudi,&nbsp;Srikala Rajala,&nbsp;Narasimha Rao Gaddam,&nbsp;Gomathi Swaminathan,&nbsp;Jaya Preethi Peesa,&nbsp;Kalirajan Rajagopal,&nbsp;Mohammed Afzal Azam","doi":"10.2174/1573409919666221230105758","DOIUrl":"https://doi.org/10.2174/1573409919666221230105758","url":null,"abstract":"<p><strong>Background: </strong>The south Indian Telugu states will celebrate a new year called 'Ugadi' which is a south Indian traditional festival. The ingredients used in ugadi pachadi have often also been used in food as well as traditional Ayurveda and Siddha medicinal preparations. Coronaviruses (CoVs) are a diverse family of enveloped positive-sense single-stranded RNA viruses which can infect humans and have the potential to cause large-scale outbreaks.</p><p><strong>Objective: </strong>Considering the benefits of ugadi pachadi, we investigated the binding modes of various phytochemical constituents reported from its ingredients against five targets of SARS-CoV-2.</p><p><strong>Methods: </strong>Flexible-ligand docking simulations were achieved through AutoDock version 1.5.6. Following 50ns of molecular dynamics simulation using GROMACS 2018.1 software and binding free energy (ΔG_bind) of the protein-ligand complexes were calculated using the g_mmpbsa tool. ADME prediction was done using Qikprop of Schrodinger.</p><p><strong>Results: </strong>From the molecular docking and MM/PBSA results compound Eriodictin exhibited the highest binding energy when complexed with nucleocapsid N protein (6M3M) (-6.8 kcal/mol, - 82.46 kJ/mol), bound SARS-CoV-2-hACE2 complex (6M0J) (-7.4 kcal/mol, -71.10 kJ/mol) and Mpro (6XR3) (-8.6 kcal/mol, -140.21 kJ/mol). Van der Waal and electrostatic energy terms highly favored total free energy binding.</p><p><strong>Conclusion: </strong>The compounds Eriodictin, Vitexin, Cycloart-3, 24, 27-triol, Agigenin, Mangiferin, Mangiferolic acid, Schaftoside, 27-Hydroxymangiferonic acid, Quercetin, Azadirachtol, Cubebin, Isomangiferin, Isoquercitrin, Malicarpin, Orientin and procyanidin dimer exhibited satisfactory binding energy values when compared with standard molecules. The further iterative optimization of high-ranked compounds following validation by in vitro and in vivo techniques assists in discovering therapeutic anti-SARS-CoV-2 molecules.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 3","pages":"202-233"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9818136","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":"Neural Network-based Optimization of <i>Silybum Marianum</i> Extract-loaded Chitosan Particles: Modeling, Preparation and Antioxidant Evaluation.","authors":"Ali Hanafi, Kazem D Safa, Shamsali Rezazadeh","doi":"10.2174/1573409918666221010101036","DOIUrl":"10.2174/1573409918666221010101036","url":null,"abstract":"<p><strong>Background: </strong>Silymarin is a flavonolignan extracted from Silybum marianum with various therapeutic applications. Many studies have focused on improving the bioavailability of silymarin due to its wide range of efficacy and low bioavailability. Chitosan, a naturally occurring polymeric substance, has a strong reputation for increasing the solubility of poorly soluble compounds.</p><p><strong>Objective: </strong>This study used artificial neural networks (ANNs) to measure the effects of pH, chitosan to silymarin ratio, chitosan to tripolyphosphate ratio, and stirring time on the loading efficiency of silymarin into chitosan particles.</p><p><strong>Methods: </strong>A model was developed to investigate the interactions between input factors and silymarin loading efficiency. The DPPH method was utilized to determine the antioxidant activity of an optimized formula and pure raw materials.</p><p><strong>Results: </strong>According to the outcome of the ANN model, pH and the chitosan to silymarin ratio demonstrated significant effects on loading efficiency. In addition, increased stirring time decreased silymarin loading, whereas the chitosan-to-tripolyphosphate ratio showed a negligible effect on loading efficiency.</p><p><strong>Conclusion: </strong>Maximum loading efficiency occurred at a pH of approximately~5. Moreover, silymarin- loaded chitosan particles with a lower IC₅₀ value (36.17 ± 0.02 ppm) than pure silymarin (165.04 ± 0.07 ppm) demonstrated greater antioxidant activity.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 1","pages":"2-12"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469972","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":"Network Analysis of Anti-inflammatory Phytochemicals and Omics Data for Rheumatoid Arthritis.","authors":"Bharathi Nathan,&nbsp;Archana Prabahar,&nbsp;Sudheer Mohammed","doi":"10.2174/1573409919666230106125058","DOIUrl":"https://doi.org/10.2174/1573409919666230106125058","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that affects the synovial joints. Nearly 1.6 billion patients are affected by RA worldwide and the incidence of RA is about 0.5 to 1%. Recent studies reveal that immune cell responses and secretion of inflammatory factors are important for the control of RA.</p><p><strong>Methods: </strong>In this study, a set of 402 phytochemicals with anti-inflammatory properties and 16 target proteins related to anti-inflammatory diseases were identified from the literature and they were subjected to network analysis. The protein-protein interaction (PPI) network was constructed using STRING (Search Tool for the Retrieval of Interacting Genes database) database. Visualization of the target gene-phytochemical network and its protein-protein interaction network was conducted using Cytoscape and further analyzed using MCODE (Molecular Complex Detection). The gene ontology and KEGG pathway analysis was performed using DAVID tool.</p><p><strong>Results: </strong>Our results from the network approach indicate that the phytochemicals such as Withanolide, Diosgenin, and Butulin could act as potential substitute for anti-inflammatory drugs, including DMARDs. Genes such as Mitogen-activated protein kinase (MAPK) and Interleukin were found as hub genes and acted as best inhibitors for the target protein pathways. Curcumin, Catechin was also found to be involved in various signaling pathways such as NF-kappa B signaling pathway, ErbB signaling pathway and acted as the best inhibitor along with other candidate phytochemicals.</p><p><strong>Conclusion: </strong>In the current study, we were able to identify Withanolide, Diosgenin, and Butulin as potential anti-inflammatory phytochemicals and determine their association with key pathways involved in RA through network analysis. We hypothesized that natural compounds could significantly contribute to the reduction of dosage, improve the treatment and act as a therapeutic agent for more economical and safer treatment of RA.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 5","pages":"356-366"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9473511","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}