Current drug discovery technologies最新文献

{"title":"Protective Effects of Chrysin on Hippocampal Damage Induced by Chlorpyrifos in Adult Rats.","authors":"Behzad Mesbahzadeh,&nbsp;Abolfazl Hatami-Moghaddam,&nbsp;Kobra Naseri,&nbsp;Amir Masoud Jafari-Nozad,&nbsp;Saeed Samarghandian,&nbsp;Tahereh Farkhondeh","doi":"10.2174/1570163820666230302093111","DOIUrl":"https://doi.org/10.2174/1570163820666230302093111","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the possible effects of chlorpyrifos on the rat hippocampus and evaluate whether these effects can be decreased with chrysin co-administration in an animal model.</p><p><strong>Methods: </strong>Male Wistar rats were randomly divided into 5 groups; Control (C), Chlorpyrifos (CPF), Chlorpyrifos + Chrysin (12.5 mg/kg) (CPF + CH1), Chlorpyrifos + Chrysin (25 mg/kg) (CPF + CH2), Chlorpyrifos + Chrysin (50 mg/kg) (CPF + CH3). After 45 days, hippocampus tissues were evaluated by biochemical and histopathological tests.</p><p><strong>Results: </strong>Biochemical findings indicated that CPF and CPF plus CH administration could not significantly change SOD activity, and MAD, GSH, and NO levels in the hippocampus tissue of animals versus controls. Histopathological findings of the toxic effects of CPF on hippocampus tissue as evidenced by inflammatory cell infiltration, degeneration/necrosis, and mild hyperemia. CH could ameliorate these histopathological changes in a dose-dependent manner.</p><p><strong>Conclusion: </strong>In conclusion, CH was effective against histopathological damage induced by CPF in the hippocampus through modulating inflammation and apoptosis.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 4","pages":"e020323214241"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Effects and Side Effects of Two Antipsychotic Drugs in the Treatment of Children and Adolescents with Tourette Syndrome: A Semi-experimental Research.","authors":"Atefeh Soltanifar,&nbsp;Raheleh Lashkarnevis,&nbsp;Maliheh Ziaee,&nbsp;Fatemeh Moharari,&nbsp;Roya Samadi,&nbsp;Azadeh Soltanifar,&nbsp;Maedeh Kamrani","doi":"10.2174/1570163820666230609095720","DOIUrl":"10.2174/1570163820666230609095720","url":null,"abstract":"<p><strong>Introduction: </strong>Due to the high prevalence of Tourette's disorder among children and adolescents and its negative consequences, an appropriate and effective medical treatment with minimal complications is necessary. Therefore, this study was conducted to compare the effects of Aripiprazole and Risperidone on Tourette's disorders in children and adolescents.</p><p><strong>Methods: </strong>The statistical population of this semi-experimental study was children and adolescents aged seven to eighteen years old. They were diagnosed with Tourette's disorder based on the DSM-V criteria by the clinical interview of a child and adolescent psychiatrist in the child Psychiatry clinic of Ibne- Sina's Psychiatric Hospital (Mashhad-Iran) in 2018. A total of forty participants were selected by the convenience sampling method, and they were randomly divided into two groups treated with medicines, Risperidone or Aripiprazole, for two months. Then, the demographic information questionnaire was completed. The Y-GTSS Scale was completed. The clinical Effect Rating Scale (CGI-Tics Scale) was completed. Calculation of body mass index and medical side effects complications were completed. The evaluation was carried out at the beginning and on the second, fourth, and eighth weeks, and the results were compared. The data were analyzed using SPSS software. 14, descriptive statistics, Chi-square, and variance analysis.</p><p><strong>Results: </strong>The two groups were homogeneous in terms of demographic variables and body mass index. Despite the positive effect of both medicines, no significant difference was observed among the general scores of such disorders, the overall score of severity, Tourette's recovery, and BMI of these two groups at the intervals and the end of treatments. (p <0.05). Due to the low number of complications reported, statistical comparisons of the medical side effects were not made.</p><p><strong>Conclusion: </strong>According to the results, the two medicines, Aripiprazole and Risperidone, effectively improved the symptoms of Tourette's disorder and its overall severity. However, there were no significant statistical differences between them. Furthermore, in terms of the medical side effects, the statistical comparison between the two medicines was impossible due to the small number of complications.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9612353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Biological Activity Evaluation of Pyrazole-1,2,4-triazole Hybrids: A Computer-aided Docking Studies.","authors":"Naga Mohan Mallisetty,&nbsp;Hanumantharao Ganipisetti,&nbsp;Debendra Majhi,&nbsp;Raju Sirisilla,&nbsp;Venkata Nagendra Kumar Putta","doi":"10.2174/1570163820666221125121625","DOIUrl":"https://doi.org/10.2174/1570163820666221125121625","url":null,"abstract":"<p><strong>Background: </strong>In the present study, a new series of 1,2,4-triazole linked to pyrazole derivatives (8a-j) of 4-(((7-amino-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl- 2-phenyl-1H-pyrazol-3(2H)-one were synthesized and assessed for their antibacterial and anticancer activity.</p><p><strong>Objective: </strong>Encouraged by these results, these analogues 4-(((7-amino-7H-[1,2,4]triazolo[4,3- b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-ones 8 have been synthesized and their inhibitory potential activity against different bacterial microorganisms and cancer cell lines was discussed.</p><p><strong>Methods: </strong>All the synthesized final scaffolds were characterized by ¹H NMR, ¹³C NMR, IR, mass and elemental analysis. All the synthesized 1,2,4-triazole linked to pyrazole compounds were evaluated for their antimicrobial sensitivity by using the agar dilution technique. The anticancer activity of these compounds has been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and docking results are described by Autodock 4.2.</p><p><strong>Results: </strong>In vitro analysis suggests that compounds 8h, 8f, and 8b demonstrated excellent antibacterial activity against S. aureus, P. aeruginosa, S. epidermidis with MICs of 8, 8, 11 μg/mL respectively, while the remaining compounds showed moderate to good inhibitory potential. Some of them exhibited potent cytotoxicity against MCF-7 and P388 cancer cell lines and compounds 8c, 8f, and 8d reveal the highest potency against MCF-7 with IC₅₀ values 2.8 ± 0.4, 3.1 ± 0.4, 3.5 ± 0.2 μM, respectively. Especially 8c, 8i and 8f showed better interaction patterns with amino acids Ala197 (N-N), Lys168 (N-N), Asn163 (O-N) at 3.13, 3.09, 3.00 A° as reported in DNA (Topo II) complex (1ZXM).</p><p><strong>Conclusion: </strong>New findings have established the fact that fused 1,2,4-triazoles linked to pyrazole contributed great significance in the field of medicinal chemistry due to their various biological properties.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 2","pages":"e251122211263"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Biological Evaluation of Some New Chalcone Derivatives as Anti-inflammatory Agents.","authors":"Zia Ur Rehman,&nbsp;Pooja Saini,&nbsp;Sushil Kumar","doi":"10.2174/1570163819666220613153225","DOIUrl":"https://doi.org/10.2174/1570163819666220613153225","url":null,"abstract":"<p><strong>Aim: </strong>The present research work aims to prepare a series of 1-(4-(2-(1H-indol-1-yl)-2- oxoethoxy)phenyl)-3-phenylprop-2-en-1-one derivatives.</p><p><strong>Methods: </strong>The major compound was achieved by the reaction of indole with chloroacetylchloride in benzene afforded 2-chloro-1-(indoline-1-yl) ethanone which reacts o- hydroxy acetophenone in presence of acetonitrile to form 2-(4-acetylphenoxy)-1-(1H-indol-1-yl)ethan-1-one then goes through aldol condensation to give various final derivatives.</p><p><strong>Results and conclusion: </strong>After the synthesis of compounds, the synthesized compounds were characterized by checking their solubility, melting point, thin layer chromatography, IR, 1HNMR spectral data and elemental analysis. All of the prepared derivatives were evaluated for their anti-inflammatory activity on wistar albino rats by following the carrageenan-induced Rat Hind Paw Edema model.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 1","pages":"e130622205910"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9832802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of the Therapeutic Importance of Indole Scaffold in Drug Discovery.","authors":"Nishith Teraiya,&nbsp;Khushbu Agrawal,&nbsp;Tarun M Patel,&nbsp;Archita Patel,&nbsp;Samir Patel,&nbsp;Umang Shah,&nbsp;Shaileshkumar Shah,&nbsp;Khushman Rathod,&nbsp;Krupa Patel","doi":"10.2174/1570163820666230505120553","DOIUrl":"10.2174/1570163820666230505120553","url":null,"abstract":"<p><p>Indole is known as a versatile heterocyclic building block for its multiple pharmacological activities and has a high probability of success in the race for drug candidates. Many natural products, alkaloids, and bioactive heterocycles contain indole as the active principle pharmacophore. These encourage the researchers to explore it as a lead in the drug development process. The current manuscript will serve as a torchbearer for understanding the structurally diverse class of indole derivatives with extensive pharmacological activity. The current manuscript describes the intermediates and their functional groups responsible for superior biological activity compared to the standard. The review is written to help researchers to choose leads against their target but also to provide crucial insight into the design of a hybrid pharmacophore-based approach in drug design with enhanced potential. The present reviews on the indole derivatives correlate the structures with biological activities as well as essential pharmacophores, which were highlighted. The discussion was explored under challenging targets like dengue, chikungunya (anti-viral), antihypertensive, diuretic, immunomodulator, CNS stimulant, antihyperlipidemic, antiarrhythmic, anti-Alzheimer's, and neuroprotective, along with anticancer, antitubercular, antimicrobial, anti-HIV, antimalarial, anti-inflammatory, antileishmanial, antianthelmintic, and enzyme inhibitors. So, this review includes a discussion of 19 different pharmacological targets for indole derivatives that could be utilized to derive extensive information needed for ligand-based drug design. The article will guide the researchers in the selection, design of lead and pharmacophore, and ligand-based drug design using indole moiety.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"9-37"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9480357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In-Silico</i> Designing of a Multi-Epitope Vaccine against SARS-CoV2 and Studying the Interaction of the Vaccine with Alpha, Beta, Delta and Omicron Variants of Concern.","authors":"Aranya Pal,&nbsp;Nibedita Pyne,&nbsp;Santanu Paul","doi":"10.2174/1570163819666220909114900","DOIUrl":"https://doi.org/10.2174/1570163819666220909114900","url":null,"abstract":"<p><strong>Background: </strong>The sudden appearance of the SARS-CoV2 virus has almost changed the future of vaccine development. There have been many different approaches to vaccination; among them, computational vaccinology in the form of multi-epitope vaccines with excellent immunological properties and minimal contamination or other adverse reactions has emerged as a promising strategy with a lot of room for further study in this area.</p><p><strong>Objective: </strong>Designing a multi-epitope vaccine from the spike protein of SARS-CoV2 based on immunoinformatics and in-silico techniques. Evaluating the binding affinity of the constructed vaccine against the major variants of concern (alpha, beta, delta, and omicron) using docking studies.</p><p><strong>Methods: </strong>The potential antigenic, immunogenic, and non-allergic T-cell epitopes were thoroughly explored using IEDB, NetCTL1.2, and NetMHCII pan 3.2 servers. The best suitable linker was identified using the ExPASy Protparam tool and VERIFY 3D. The 3D model of the vaccine was developed by RaptorX and the model was validated using ERRAT, Z-score, and Ramachandran Plot. Docking studies of the vaccine with TLR-2, 3, 4, and 7 and alpha, beta, delta, and omicron variants were performed using HADDOCK 2.4.</p><p><strong>Results: </strong>The vaccine construct showed good antigenic and immunogenic scores and was non-allergic as well. The model was capable of binding to all four selected Toll-like receptors. Docking scores with variants were also promising.</p><p><strong>Conclusion: </strong>All the variants showed good binding ability with the vaccine construct. Interaction with the alpha variant was found to be the most intense, followed by delta, beta, and omicron.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 1","pages":"e090922208713"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9774472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Molecular Structural Requirements of Flavonoids as Beta- Secretase-1 Inhibitors Using Molecular Modeling Studies.","authors":"Uttam A More,&nbsp;M N Noolvi,&nbsp;Devendra Kumar,&nbsp;Avanish Tripathi","doi":"10.2174/1570163820666230329090424","DOIUrl":"https://doi.org/10.2174/1570163820666230329090424","url":null,"abstract":"<p><strong>Background: </strong>BACE1 (beta-site amyloid precursor protein (APP) cleaving enzyme) is a key target for Alzheimer's disease research because it catalyses the rate-limiting step in the formation of amyloid protein (Aβ). Natural dietary flavonoids have gained a lot of interest as potential Alzheimer's therapy candidates because of their anti-amyloidogenic, antioxidative, and anti-inflammatory properties. More research is needed, however, to learn more about the specific routes through which flavonoids may have neuroprotective benefits in Alzheimer's disease.</p><p><strong>Objective: </strong>Here, we report an in silico molecular modeling study for natural compounds, particularly flavonoids, as BACE-1 inhibitors.</p><p><strong>Methods: </strong>The interactions of flavonoids with the BACE-1 catalytic core were disclosed by demonstrating the predicted docking pose of flavonoids with BACE-1. The stability of flavonoids BACE-1 complex was analyzed by molecular dynamic simulation (standard dynamic cascade).</p><p><strong>Results: </strong>Our findings imply that these flavonoids, which have methoxy group instead of hydroxy may be promising BACE1 inhibitors that could reduce Aβ formation in Alzheimer's disease. The molecular docking study revealed that flavonoids e bind with the BACE1's wide active site along with the catalytic residues Asp32 and Asp228. Further molecular dynamic investigation revealed that the average RMSD for all complexes ranged from 2.05 to 2.32 Å, indicating that the molecules were relatively stable during MD simulation. The RMSD analyses demonstrate that the flavonoids were structurally stable during the MD simulation. The RMSF was utilised to study the time-dependent fluctuation of the complexes. The N-terminal (~2.5 Å) fluctuates less than the C-terminal (~6.5 Å). Rutin and Hesperidin were highly stable in the catalytic region as compared to other flavonoids like Rhoifolin, Hesperidin, Methylchalcone, Phlorizin and Naringin.</p><p><strong>Conclusion: </strong>We were able to justify the flavonoids' selectivity for BACE-1 and crossing BBB for the treatment of Alzheimer's disease by using a combination of molecular modelling tools.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 3","pages":"e290323215095"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10153944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Antifungal Effect of the Essential Oil of <i>Thymus eriocalyx</i> on Dominant Filamentous Fungal Agents Isolated from Livestock and Poultry Feed.","authors":"Abdelnasser Mohammadi,&nbsp;Sima Shiravand,&nbsp;Fatemeh Saleh,&nbsp;Mohammad Yarahmadi,&nbsp;Asghar Sepahvand","doi":"10.2174/1570163820666230222093118","DOIUrl":"https://doi.org/10.2174/1570163820666230222093118","url":null,"abstract":"<p><strong>Background: </strong>One of the most important principles in disease control is the health of livestock and poultry feed. Given the natural growth of Th. eriocalyx in Lorestan province, its essential oil can be added to the livestock and poultry feed and prevent the growth of the dominant filamentous fungi.</p><p><strong>Objective: </strong>Therefore, this study aimed to identify the dominant moldy fungal agents of livestock and poultry feed, examine phytochemical compounds and analyze antifungal effects, anti-oxidant properties, as well as cytotoxicity against human white blood cells in Th. eriocalyx.</p><p><strong>Methods: </strong>Sixty samples were collected in 2016. The PCR test was used to amplify ITS1 and ASP1 regions. The analysis of essential oil was conducted by gas chromatography and gas chromatographymass spectrometry devices. MIC and MFC were performed using the broth micro-dilution method. For the analysis of DDPH activity, DDPH was used. Cytotoxicity effect on healthy human lymphocytes was carried out by the MTT method.</p><p><strong>Results: </strong>In this study, A. niger, F. verticilloides and F. circinatum, P. oxalicum, and P. chrysogenum were the most resistant species, and A. oryzae and A. fumigatus, F. prolifratum and F. eqiseti, P. janthnellum were the most susceptible ones. IC₅₀ value of T. daenensis Celak was 41.33 μg/ml, and 100 μl/ml of the essential oil caused slight cell lysis.</p><p><strong>Conclusion: </strong>Considering our results, compared with drugs and chemical additives, essential oils can be added to livestock and poultry feed to prevent the growth of filamentous fungi in the livestock and poultry feed.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 4","pages":"e220223213880"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9778303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems Pharmacology and Pharmacokinetics Strategy to Decode Bioactive Ingredients and Molecular Mechanisms from <i>Zingiber officinale</i> as Phyto-therapeutics against Neurological Diseases.","authors":"Pavan Gollapalli, Aditya S J Rao, Hanumanthappa Manjunatha, Gnanasekaran Tamizh Selvan, Praveenkumar Shetty, Nalilu Suchetha Kumari","doi":"10.2174/1570163819666220825141356","DOIUrl":"10.2174/1570163819666220825141356","url":null,"abstract":"<p><strong>Background: </strong>The bioactive constituents from Zingiber officinale (Z. officinale) have shown a positive effect on neurodegenerative diseases like Alzheimer's disease (AD), which manifests as progressive memory loss and cognitive impairment.</p><p><strong>Objective: </strong>This study investigates the binding ability and the pharmaco-therapeutic potential of Z. officinale with AD disease targets by molecular docking and molecular dynamic (MD) simulation approaches.</p><p><strong>Methods: </strong>By coupling enormous available phytochemical data and advanced computational technologies, the possible molecular mechanism of action of these bioactive compounds was deciphered by evaluating phytochemicals, target fishing, and network biological analysis.</p><p><strong>Results: </strong>As a result, 175 bioactive compounds and 264 human target proteins were identified. The gene ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis and molecular docking were used to predict the basis of vital bioactive compounds and biomolecular mechanisms involved in the treatment of AD. Amongst selected bioactive compounds, 10- Gingerdione and 1-dehydro-[8]-gingerdione exhibited significant anti-neurological properties against AD targeting amyloid precursor protein with docking energy of -6.0 and -5.6, respectively.</p><p><strong>Conclusion: </strong>This study suggests that 10-Gingerdione and 1-dehydro-[8]-gingerdione strongly modulates the anti-neurological activity and are associated with pathological features like amyloid-β plaques and hyperphosphorylated tau protein are found to be critically regulated by these two target proteins. This comprehensive analysis provides a clue for further investigation of these natural compounds' inhibitory activity in drug discovery for AD treatment.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 1","pages":"e250822207996"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9780097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Analysis to Predict Drug Targets for the Therapeutic Management of <i>Mycobacterium avium</i> sub. <i>Paratuberculosis</i>.","authors":"Taruna Mohinani,&nbsp;Aditya Saxena,&nbsp;Shoor Vir Singh","doi":"10.2174/1570163820666230310140613","DOIUrl":"https://doi.org/10.2174/1570163820666230310140613","url":null,"abstract":"<p><strong>Background: </strong>Mycobacterium avium sp. paratuberculosis (MAP) is a pathogen, which causes paratuberculosis in animals; it has also been found to be associated with a number of autoimmune disorders in humans. The emergence of drug resistance has also been found in this bacillus during disease management.</p><p><strong>Objective: </strong>The present study's focus was to identify potential therapeutic targets for the therapeutic management of Mycobacterium avium sp. paratuberculosis infection by in silico analysis.</p><p><strong>Methods: </strong>Differentially-expressed genes (DEGs) can be good drug targets, which can be identified from microarray studies. We used gene expression profile GSE43645 to identify differentiallyexpressed genes. An integrated network of upregulated DEGs was constructed with the STRING database and the constructed network was analyzed and visualized by Cytoscape. Clusters in the proteinprotein interaction (PPI) network were identified by the Cytoscape app ClusterViz. MAP proteins predicted in clusters were analyzed for their non-homology with the human proteins, and homologous proteins were excluded. Essential proteins and cellular localization analysis and the physicochemical characteristics prediction were also done. Finally, the druggability of the target proteins and drugs that can block the targets was predicted using the DrugBank database and confirmed by molecular docking. Structural prediction and verification of drug target proteins were also carried out.</p><p><strong>Results: </strong>Two drug targets, MAP_1210 (inhA) and MAP_3961 (aceA), encoding enoyl acyl carrier protein reductase and isocitrate lyase enzymes, respectively, were finally predicted as potential drug targets.</p><p><strong>Conclusion: </strong>Both of these proteins have been predicted as drug targets in other mycobacterial species also, supporting our results. However, further experiments are required to confirm these results.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 4","pages":"e100323214551"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}