{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:24:46Z","timestamp":1779927886871,"version":"3.53.1"},"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Schistosomiasis, also known as bilharzia or snail fever, is a tropical parasitic disease resulting from flatworms of the Schistosoma genus. This often overlooked disease has significant impacts in affected regions, causing enduring morbidity, hindering child development, reducing productivity, and creating economic burdens. Praziquantel (PZQ) is currently the only treatment option for schistosomiasis. Given the potential rise of drug resistance and the limited treatment choices available, there is a need to develop more effective inhibitors for this neglected tropical disease (NTD). In view of this, quantitative structure-activity relationship studies (QSAR), molecular docking, molecular dynamics simulations, drug-likeness, and ADMET predictions were applied to 31 inhibitors of Schistosoma mansoni Dihydroorotate dehydrogenase (SmDHODH). The designed QSAR model demonstrated robust statistical parameters including an R<jats:sup>2<\/jats:sup> of 0.911, R<jats:sup>2<\/jats:sup><jats:sub>adj<\/jats:sub> of 0.890, Q<jats:sup>2<\/jats:sup>cv of 0.686, R<jats:sup>2<\/jats:sup><jats:sub>pred<\/jats:sub> of 0.807, and cR<jats:sup>2<\/jats:sup>p of 0.825, confirming its robustness. Compound <jats:bold>26<\/jats:bold>, identified as the most active derivative, emerged as a lead candidate for new potential inhibitors through ligand-based drug design. Subsequently, 12 novel compounds (<jats:bold>26A<\/jats:bold>-<jats:bold>26L<\/jats:bold>) were designed with enhanced inhibition activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding and hydrophobic interactions, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (\u0394G<jats:sub>bind<\/jats:sub>) calculations validated the stability of the two best-designed molecules (<jats:bold>26A<\/jats:bold> and <jats:bold>26L<\/jats:bold>). Furthermore, drug-likeness and ADMET prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for treating schistosomiasis.<\/jats:p>","DOI":"10.1371\/journal.pntd.0012453","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T17:23:10Z","timestamp":1726161790000},"page":"e0012453","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Computer-aided discovery of novel SmDHODH inhibitors for schistosomiasis therapy: Ligand-based drug design, molecular docking, molecular dynamic simulations, drug-likeness, and ADMET studies"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9261-4641","authenticated-orcid":true,"given":"Saudatu Chinade","family":"Ja\u2019afaru","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adamu","family":"Uzairu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharika","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Hamid","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed Sani","family":"Sallau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Iloegbulam","family":"Ndukwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Tukur","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imren","family":"Bayil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2954-3215","authenticated-orcid":true,"given":"Abu Tayab","family":"Moin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"pntd.0012453.ref001","article-title":"Schistosomiasis","author":"WHO","year":"2023"},{"issue":"3","key":"pntd.0012453.ref002","article-title":"Schistosomiasis with a Focus on Africa","volume":"6","author":"OP Aula","year":"2021","journal-title":"Tropical medicine and infectious disease"},{"issue":"7","key":"pntd.0012453.ref003","doi-asserted-by":"crossref","first-page":"e0009628","DOI":"10.1371\/journal.pntd.0009628","article-title":"Prevalence of urogenital and intestinal schistosomiasis among school children in South-west Nigeria.","volume":"15","author":"JA Ojo","year":"2021","journal-title":"PLoS neglected tropical diseases."},{"key":"pntd.0012453.ref004","doi-asserted-by":"crossref","first-page":"635869","DOI":"10.3389\/fimmu.2021.635869","article-title":"Schistosomiasis morbidity hotspots: roles of the human host, the parasite and their interface in the development of severe morbidity","volume":"12","author":"PA Mawa","year":"2021","journal-title":"Frontiers in immunology"},{"key":"pntd.0012453.ref005","doi-asserted-by":"crossref","first-page":"642383","DOI":"10.3389\/fimmu.2021.642383","article-title":"Schistosomiasis drug discovery in the era of automation and artificial intelligence","volume":"12","author":"JT Moreira-Filho","year":"2021","journal-title":"Frontiers in immunology"},{"key":"pntd.0012453.ref006","first-page":"3","article-title":"A review of the genetic determinants of praziquantel resistance in Schistosoma mansoni: Is praziquantel and intestinal schistosomiasis a perfect match?","author":"S Summers","year":"2022","journal-title":"Frontiers in Tropical Diseases."},{"issue":"7","key":"pntd.0012453.ref007","doi-asserted-by":"crossref","first-page":"130378","DOI":"10.1016\/j.bbagen.2023.130378","article-title":"Kinetic and structural studies of Mycobacterium tuberculosis dihydroorotate dehydrogenase reveal new insights into class 2 DHODH inhibition","volume":"1867","author":"O Teixeira","year":"2023","journal-title":"Biochimica et biophysica acta General subjects"},{"issue":"3","key":"pntd.0012453.ref008","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3390\/molecules29030635","article-title":"Drug Repurposing in the Chemotherapy of Infectious Diseases.","volume":"29","author":"A Hamid","year":"2024","journal-title":"Molecules."},{"issue":"1","key":"pntd.0012453.ref009","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40170-021-00250-z","article-title":"DHODH and cancer: promising prospects to be explored.","volume":"9","author":"Y Zhou","year":"2021","journal-title":"Cancer & metabolism"},{"issue":"3","key":"pntd.0012453.ref010","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/febs.15367","article-title":"Structural basis for the function and inhibition of dihydroorotate dehydrogenase from Schistosoma mansoni","volume":"288","author":"RM de Mori","year":"2021","journal-title":"The FEBS Journal"},{"issue":"8","key":"pntd.0012453.ref011","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.2174\/1570159X15666170102145257","article-title":"Advantages of Structure-Based Drug Design Approaches in Neurological Disorders.","volume":"15","author":"M Aarthy","year":"2017","journal-title":"Current neuropharmacology"},{"issue":"5","key":"pntd.0012453.ref012","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.jtumed.2023.01.013","article-title":"Virtual screening, pharmacokinetic, and DFT studies of anticancer compounds as potential V600E-BRAF kinase inhibitors","volume":"18","author":"AB Umar","year":"2023","journal-title":"Journal of Taibah University Medical Sciences"},{"key":"pntd.0012453.ref013","first-page":"1","article-title":"Structure-Based Design of Potential Anti-schistosomiasis Agent Targeting SmHDAC8: An In Silico Approach Utilizing QSAR, MD Simulation and ADMET Prediction","author":"SC Ja\u2019afaru","year":"2023","journal-title":"Chemistry Africa"},{"key":"pntd.0012453.ref014","first-page":"155","article-title":"A search for novel antidiabetic agents using ligand-based drug design and molecular docking studies employing human intestinal maltase-glucoamylase as model enzyme","author":"KS Aminu","year":"2023","journal-title":"Adv J Chem A"},{"issue":"5","key":"pntd.0012453.ref015","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.jtumed.2023.02.015","article-title":"Pharmacokinetic profiling of quinazoline-4(3H)-one analogs as EGFR inhibitors: 3D-QSAR modeling, molecular docking studies and the design of therapeutic agents.","volume":"18","author":"SH Abdullahi","year":"2023","journal-title":"Journal of Taibah University Medical Sciences"},{"key":"pntd.0012453.ref016","article-title":"Molecular docking studies of some benzoxazole and benzothiazole derivatives as VEGFR-2 target inhibitors: In silico design, MD simulation, pharmacokinetics and DFT studies.","author":"SH Abdullahi","year":"2023","journal-title":"Intelligent Pharmacy."},{"issue":"1","key":"pntd.0012453.ref017","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s43046-023-00182-3","article-title":"Ligand-based drug design of quinazolin-4(3H)-ones as breast cancer inhibitors using QSAR modeling, molecular docking, and pharmacological profiling.","volume":"35","author":"SH Abdullahi","year":"2023","journal-title":"Journal of the Egyptian National Cancer Institute."},{"key":"pntd.0012453.ref018","unstructured":"ChEMBL. 2023 [cited 2023. Available from: https:\/\/www.ebi.ac.uk\/chembl\/web_components\/explore\/activities\/STATE_ID:frSQLTZmy7I3wLNMbVAXGw==."},{"key":"pntd.0012453.ref019","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.biochi.2019.01.006","article-title":"Structural basis for the design of selective inhibitors for Schistosoma mansoni dihydroorotate dehydrogenase","volume":"158","author":"MC Nonato","year":"2019","journal-title":"Biochimie"},{"key":"pntd.0012453.ref020","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ejmech.2019.02.018","article-title":"Ligand-based design, synthesis and biochemical evaluation of potent and selective inhibitors of Schistosoma mansoni dihydroorotate dehydrogenase","volume":"167","author":"FA Calil","year":"2019","journal-title":"European journal of medicinal chemistry"},{"key":"pntd.0012453.ref021","doi-asserted-by":"crossref","first-page":"102787","DOI":"10.1016\/j.bcab.2023.102787","article-title":"Computational design of quinoxaline molecules as VEGFR-2 inhibitors: QSAR modelling, pharmacokinetics, molecular docking, and dynamics simulation studies","volume":"51","author":"SH Abdullahi","year":"2023","journal-title":"Biocatalysis and Agricultural Biotechnology"},{"key":"pntd.0012453.ref022","doi-asserted-by":"crossref","first-page":"100132","DOI":"10.1016\/j.chphi.2022.100132","article-title":"Quantitative Structure-Activity Relationship, Structure-based Design, and ADMET studies of pyrimethamine and cycloguanil analogs inhibitors of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS).","volume":"5","author":"Z Ya\u2019u Ibrahim","year":"2022","journal-title":"Chemical Physics Impact"},{"issue":"2","key":"pntd.0012453.ref023","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jtumed.2022.09.002","article-title":"2D-QSAR, molecular docking, drug-likeness, and ADMET\/pharmacokinetic predictions of some non-small cell lung cancer therapeutic agents","volume":"18","author":"MT Ibrahim","year":"2023","journal-title":"Journal of Taibah University Medical Sciences"},{"key":"pntd.0012453.ref024","first-page":"1104","article-title":"Tool development for Prediction of pIC50 values from the IC50 values-A pIC50 value calculator","volume":"5","author":"C Selvaraj","year":"2011","journal-title":"Current Trends in Biotechnology and Pharmacy"},{"issue":"7","key":"pntd.0012453.ref025","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1002\/jcc.21707","article-title":"PaDEL-descriptor: an open source software to calculate molecular descriptors and fingerprints","volume":"32","author":"CW Yap","year":"2011","journal-title":"J Comput Chem"},{"issue":"4","key":"pntd.0012453.ref026","doi-asserted-by":"crossref","first-page":"953","DOI":"10.3390\/cells10040953","article-title":"The Impact of Preprocessing Methods for a Successful Prostate Cell Lines Discrimination Using Partial Least Squares Regression and Discriminant Analysis Based on Fourier Transform Infrared Imaging.","volume":"10","author":"D Liberda","year":"2021","journal-title":"Cells"},{"issue":"3","key":"pntd.0012453.ref027","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1021\/ci060031z","article-title":"A genetic-function-approximation-based QSAR model for the affinity of arylpiperazines toward \u03b11 adrenoceptors","volume":"46","author":"L Maccari","year":"2006","journal-title":"Journal of chemical information and modeling"},{"key":"pntd.0012453.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/07391102.2023.2280735","article-title":"Molecular modelling studies of substituted indole derivatives as novel influenza a virus inhibitors","author":"M Abdullahi","year":"2023","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"pntd.0012453.ref029","first-page":"141","article-title":"Applicability Domain: A Step Toward Confident Predictions and Decidability for QSAR Modeling.","author":"S Kar"},{"key":"pntd.0012453.ref030","first-page":"26","article-title":"Principles of QSAR models validation: Internal and external.","author":"P. Gramatica","year":"2007","journal-title":"QSAR & COMBINATORIAL SCIENCE"},{"key":"pntd.0012453.ref031","article-title":"Y-Randomization\u2013A Useful Tool in QSAR Validation, or Folklore?","author":"C R\u00fccker","year":"2006"},{"issue":"3","key":"pntd.0012453.ref032","doi-asserted-by":"crossref","first-page":"102514","DOI":"10.1016\/j.jksus.2022.102514","article-title":"Modelling the Anticancer Activity of 4-Alkoxy Cinnamic Analogues using 3D-Descriptors and Genetic Algorithm-Multiple Linear Regression (GA-MLR) Method.","volume":"35","author":"H Rasyid","year":"2023","journal-title":"Journal of King Saud University\u2014Science"},{"issue":"1","key":"pntd.0012453.ref033","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s42269-022-00853-6","article-title":"Salicylic acid derivatives as potential \u03b1-glucosidase inhibitors: drug design, molecular docking and pharmacokinetic studies.","volume":"46","author":"KS Aminu","year":"2022","journal-title":"Bulletin of the National Research Centre"},{"key":"pntd.0012453.ref034","doi-asserted-by":"crossref","first-page":"100911","DOI":"10.1016\/j.cdc.2022.100911","article-title":"Ligand-based drug design, molecular docking and pharmacokinetic studies of some series of 1,4\u2014dihydropyridines derivatives as human intestinal maltase-glucoamylase inhibitor.","volume":"41","author":"KS Aminu","year":"2022","journal-title":"Chemical Data Collections"},{"key":"pntd.0012453.ref035","doi-asserted-by":"crossref","first-page":"16565","DOI":"10.1038\/s41598-023-43175-x","article-title":"Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives","volume":"13","author":"S Akash","year":"2023","journal-title":"Scientific Reports"},{"key":"pntd.0012453.ref036","first-page":"252","article-title":"Gromacs: A parallel computer for molecular dynamics simulations","volume":"92","author":"H Bekker","year":"1993","journal-title":"Physics Computing"},{"key":"pntd.0012453.ref037","first-page":"34","article-title":"CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data","author":"J Huang","year":"2013","journal-title":"Journal of computational chemistry"},{"key":"pntd.0012453.ref038","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1002\/jcc.21816","article-title":"SwissParam: A Fast Force Field Generation Tool for Small Organic Molecules","volume":"32","author":"V Zoete","year":"2011","journal-title":"Journal of computational chemistry"},{"key":"pntd.0012453.ref039","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1021\/jz501780a","article-title":"Building Water Models: A Different Approach","volume":"5","author":"S Izadi","year":"2014","journal-title":"Journal of Physical Chemistry Letters"},{"key":"pntd.0012453.ref040","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular-Dynamics with Coupling to An External Bath","volume":"81","author":"H Berendsen","year":"1984","journal-title":"The Journal of Chemical Physics"},{"issue":"11","key":"pntd.0012453.ref041","doi-asserted-by":"crossref","first-page":"7421","DOI":"10.1021\/acs.cgd.0c01098","article-title":"Molecular Dynamics Simulation of Molecular Crystals under Anisotropic Compression: Bulk and Directional Effects in Anthracene and Paracetamol.","volume":"20","author":"S Rizzato","year":"2020","journal-title":"Crystal Growth & Design."},{"key":"pntd.0012453.ref042","first-page":"18","article-title":"LINCS: A Linear Constraint Solver for molecular simulations","author":"B Hess","year":"1998","journal-title":"Journal of Computational Chemistry"},{"issue":"12","key":"pntd.0012453.ref043","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u00b7log(N) method for Ewald sums in large systems.","volume":"98","author":"T Darden","year":"1993","journal-title":"The Journal of Chemical Physics"},{"issue":"1","key":"pntd.0012453.ref044","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: visual molecular dynamics","volume":"14","author":"W Humphrey","year":"1996","journal-title":"Journal of molecular graphics"},{"issue":"1784","key":"pntd.0012453.ref045","doi-asserted-by":"crossref","first-page":"20190198","DOI":"10.1098\/rstb.2019.0198","article-title":"Three-dimensional structure of Megabalanus rosa Cement Protein 20 revealed by multi-dimensional NMR and molecular dynamics simulations.","volume":"374","author":"H Mohanram","year":"2019","journal-title":"Philosophical transactions of the Royal Society of London Series B, Biological sciences."},{"issue":"Suppl 1","key":"pntd.0012453.ref046","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/1471-2105-11-S1-S7","article-title":"Molecular dynamics simulation studies and in vitro site directed mutagenesis of avian beta-defensin Apl_AvBD2.","volume":"11","author":"SS Soman","year":"2010","journal-title":"BMC Bioinformatics."},{"key":"pntd.0012453.ref047","first-page":"21","article-title":"Stability, Hydrogen Bond Occupancy Analysis and Binding Free Energy Calculation from Flavonol Docked in DAPK1","author":"A Zikri","year":"2020","journal-title":"Active Site Using Molecular Dynamic Simulation Approaches. Indonesian Journal of Chemistry"},{"issue":"16","key":"pntd.0012453.ref048","doi-asserted-by":"crossref","first-page":"9478","DOI":"10.1021\/acs.chemrev.9b00055","article-title":"End-Point Binding Free Energy Calculation with MM\/PBSA and MM\/GBSA: Strategies and Applications in Drug Design","volume":"119","author":"E Wang","year":"2019","journal-title":"Chemical Reviews"},{"key":"pntd.0012453.ref049","doi-asserted-by":"crossref","first-page":"117793222211256","DOI":"10.1177\/11779322221125605","article-title":"Molecular Docking, Validation, Dynamics Simulations, and Pharmacokinetic Prediction of Phytochemicals Isolated From Croton dichogamus Against the HIV-1 Reverse Transcriptase","volume":"16","author":"E Terefe","year":"2022","journal-title":"Bioinformatics and Biology Insights"},{"issue":"1","key":"pntd.0012453.ref050","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1080\/2314808X.2023.2185994","article-title":"Pharmacoinformatics-based strategy in designing and profiling of some Pyrazole analogues as novel hepatitis C virus inhibitors with pharmacokinetic analysis","volume":"10","author":"S Ejeh","year":"2023","journal-title":"Egyptian Journal of Basic and Applied Sciences"},{"key":"pntd.0012453.ref051","unstructured":"OSIRIS Property Explorer 2023 [Available from: https:\/\/www.organic-chemistry.org\/prog\/peo\/."},{"issue":"1","key":"pntd.0012453.ref052","first-page":"93","article-title":"In Silico Comparison of Drug-Likeness of Phytochemicals from Nine Herbal Plants against Asthma","volume":"12","author":"T Weerakoon","year":"2022","journal-title":"Chemistry Proceedings"},{"issue":"2","key":"pntd.0012453.ref053","doi-asserted-by":"crossref","first-page":"14","DOI":"10.31643\/2023\/6445.13","article-title":"SwissADME and pkCSM webservers predictors: An integrated online platform for accurate and comprehensive predictions for in silico ADME\/T properties of artemisinin and its derivatives.","volume":"325","author":"KA Azzam","year":"2023","journal-title":"Kompleksnoe Ispolzovanie Mineralnogo Syra = Complex use of mineral resources."},{"issue":"1","key":"pntd.0012453.ref054","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"A Daina","year":"2017","journal-title":"Scientific Reports"},{"issue":"9","key":"pntd.0012453.ref055","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"DEV Pires","year":"2015","journal-title":"Journal of Medicinal Chemistry"},{"key":"pntd.0012453.ref056","doi-asserted-by":"crossref","first-page":"651","DOI":"10.12688\/f1000research.18904.1","article-title":"functional and docking analysis against Schistosoma mansoni dihydroorotate dehydrogenase for potential chemotherapeutic drugs","volume":"8","author":"Benson O. Structural","year":"2019","journal-title":"F1000Research"},{"issue":"1","key":"pntd.0012453.ref057","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s42250-020-00207-7","article-title":"QSAR, Ligand Based Design and Pharmacokinetic Studies of Parviflorons Derivatives as Anti-Breast Cancer Drug Compounds Against MCF-7 Cell Line.","volume":"4","author":"HL Abdulrahman","year":"2021","journal-title":"Chemistry Africa."},{"key":"pntd.0012453.ref058","first-page":"3","article-title":"Quantitative Structure-Activity Relationship Analysis of the Anti- tyrosine Activity of Some Tetraketone and Benzyl-benzoate Derivatives Based on Genetic Algorithm-Multiple Linear Regression.","author":"E Edache","year":"2016"},{"key":"pntd.0012453.ref059","first-page":"3","article-title":"Quantitative Structure\u2013Activity Relationship Model","author":"S Elijah Adeniji","year":"2020","journal-title":"Molecular Docking Simulation and Computational Design of Some Novel Compounds Against DNA Gyrase Receptor. Chemistry Africa"},{"key":"pntd.0012453.ref060","first-page":"1","article-title":"Discovery of new 2, 4-diaminopyrimidines derivatives as EGFRT790M kinase inhibitors: a structure-based approach with DFT calculation, drug-likeness, ADME-toxicity properties evaluation and MD simulation","author":"MT Ibrahim","year":"2024","journal-title":"Journal of Umm Al-Qura University for Applied Sciences"},{"key":"pntd.0012453.ref061","doi-asserted-by":"crossref","first-page":"e01462","DOI":"10.1016\/j.sciaf.2022.e01462","article-title":"Computational modelling of some phenolic diterpenoid compounds as anti-influenza A virus agents.","volume":"19","author":"M Abdullahi","year":"2023","journal-title":"Scientific African"},{"key":"pntd.0012453.ref062","doi-asserted-by":"crossref","first-page":"e02102","DOI":"10.1016\/j.sciaf.2024.e02102","article-title":"In silico screening, pharmacokinetic, DFT, and dynamics simulation study of ant-hepatitis C virus compounds as potential NS5B Polymerase inhibitors.","volume":"23","author":"S Ejeh","year":"2024","journal-title":"Scientific African"},{"key":"pntd.0012453.ref063","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2174\/157340912800492384","article-title":"Importance of Kier-Hall Topological Indices in the QSAR of Anticancer Drug Design.","volume":"8","author":"S Nandi","year":"2012","journal-title":"Current computer-aided drug design."},{"key":"pntd.0012453.ref064","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/ajpas\/2019\/v5i230132","article-title":"Diagnosing Multicollinearity of Logistic Regression Model","author":"N Senaviratna","year":"2019","journal-title":"Asian Journal of Probability and Statistics"},{"key":"pntd.0012453.ref065","doi-asserted-by":"crossref","first-page":"0255","DOI":"10.18540\/jcecvl4iss2pp0255-0264","article-title":"QSAR STUDIES ON DERIVATIVES OF QUINAZOLINE-4(3H)-ONES WITH ANTICONVULSANT ACTIVITIES.","volume":"4","author":"A Oluwaseye","year":"2018","journal-title":"The Journal of Engineering and Exact Sciences"},{"issue":"1","key":"pntd.0012453.ref066","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s42269-021-00690-z","article-title":"In-silico activity prediction, structure-based drug design, molecular docking and pharmacokinetic studies of selected quinazoline derivatives for their antiproliferative activity against triple negative breast cancer (MDA-MB231) cell line.","volume":"46","author":"SH Abdullahi","year":"2022","journal-title":"Bulletin of the National Research Centre."},{"issue":"2","key":"pntd.0012453.ref067","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4103\/0972-6748.62274","article-title":"Hypothesis testing, type I and type II errors","volume":"18","author":"A Banerjee","year":"2009","journal-title":"Industrial psychiatry journal"},{"key":"pntd.0012453.ref068","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.jmgm.2005.03.003","article-title":"Assessing the reliability of a QSAR model\u2019s predictions","volume":"23","author":"L He","year":"2005","journal-title":"Journal of molecular graphics & modelling"},{"issue":"1","key":"pntd.0012453.ref069","doi-asserted-by":"crossref","first-page":"e03158","DOI":"10.1016\/j.heliyon.2020.e03158","article-title":"In-silico activity prediction and docking studies of some 2, 9-disubstituted 8-phenylthio\/phenylsulfinyl-9h-purine derivatives as Anti-proliferative agents.","volume":"6","author":"MT Ibrahim","year":"2020","journal-title":"Heliyon"},{"issue":"11","key":"pntd.0012453.ref070","first-page":"1914","article-title":"2D-QSAR study of the antimicrobial activity of a series of 5-(substituted benzaldehyde) thiazolidine-2, 4-dione derivatives against Staphylococcus aureus by Multiple Linear Regression method.","volume":"11","author":"Y El Masaoudy","year":"2020","journal-title":"J Mater Environ Sci"},{"issue":"2","key":"pntd.0012453.ref071","doi-asserted-by":"crossref","first-page":"0276","DOI":"10.18540\/jcecvl4iss2pp0276-0285","article-title":"Computational studies of some biscoumarin and biscoumarin thiourea derivatives as alfa-glucosidase inhibitors","volume":"4","author":"MT Ibrahim","year":"2018","journal-title":"The Journal of Engineering and Exact Sciences"},{"issue":"5","key":"pntd.0012453.ref072","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s42452-020-2620-8","article-title":"Design of potential anti-melanoma agents against SK-MEL-5 cell line using QSAR modeling and molecular docking methods","volume":"2","author":"AB Umar","year":"2020","journal-title":"SN Applied Sciences"},{"key":"pntd.0012453.ref073","doi-asserted-by":"crossref","first-page":"133711","DOI":"10.1016\/j.molstruc.2022.133711","article-title":"Chemical diversity, biological activities and biosynthesis of fungal naphthoquinones and their derivatives: A comprehensive update","volume":"1268","author":"MA Tammam","year":"2022","journal-title":"Journal of molecular structure"},{"issue":"4","key":"pntd.0012453.ref074","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1080\/01480545.2022.2104306","article-title":"Acute and sub-acute oral toxicity assessment of 5-hydroxy-1,4-naphthoquinone in mice","volume":"46","author":"D Gohil","year":"2023","journal-title":"Drug and Chemical Toxicology"},{"issue":"9","key":"pntd.0012453.ref075","doi-asserted-by":"crossref","first-page":"14902","DOI":"10.3390\/molecules190914902","article-title":"1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling","volume":"19","author":"L-O Klotz","year":"2014","journal-title":"Molecules"},{"issue":"13","key":"pntd.0012453.ref076","article-title":"Investigation of the Relationship between Electronic Structures and Bioactivities of Polypyridyl Ru(II) Complexes.","volume":"28","author":"Z Hou","year":"2023","journal-title":"Molecules"},{"key":"pntd.0012453.ref077","doi-asserted-by":"crossref","first-page":"105895","DOI":"10.1016\/j.orgel.2020.105895","article-title":"Effect of halogenated substituent on the properties of aza-octacenes","volume":"85","author":"Y Luo","year":"2020","journal-title":"Organic Electronics"},{"issue":"1","key":"pntd.0012453.ref078","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s43094-021-00279-3","article-title":"Design of more potent quinazoline derivatives as EGFRWT inhibitors for the treatment of NSCLC: a computational approach","volume":"7","author":"MT Ibrahim","year":"2021","journal-title":"Future Journal of Pharmaceutical Sciences"},{"key":"pntd.0012453.ref079","doi-asserted-by":"crossref","first-page":"e00503","DOI":"10.1016\/j.sciaf.2020.e00503","article-title":"Structure-based design and activity modeling of novel epidermal growth factor receptor kinase inhibitors; an in silico approach","volume":"9","author":"MT Ibrahim","year":"2020","journal-title":"Scientific African"},{"key":"pntd.0012453.ref080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s42269-021-00631-w","article-title":"Chemo-informatics activity prediction, ligand based drug design, Molecular docking and pharmacokinetics studies of some series of 4, 6-diaryl-2-pyrimidinamine derivatives as anti-cancer agents.","volume":"45","author":"SH Abdullahi","year":"2021","journal-title":"Bulletin of the National Research Centre"},{"key":"pntd.0012453.ref081","first-page":"80","article-title":"The Anomalous Reactivity of Fluorobenzene in Electrophilic Aromatic Substitution and Related Phenomena.","author":"J Rosenthal","year":"2003","journal-title":"Journal of Chemical Education\u2014J CHEM EDUC"},{"issue":"1","key":"pntd.0012453.ref082","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s42269-022-00796-y","article-title":"In silico design and pharmacokinetics investigation of some novel hepatitis C virus NS5B inhibitors: pharmacoinformatics approach.","volume":"46","author":"S Ejeh","year":"2022","journal-title":"Bulletin of the National Research Centre"},{"issue":"10","key":"pntd.0012453.ref083","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.3390\/medicina57101058","article-title":"Molecular Docking and Dynamics Simulation Revealed Ivermectin as Potential Drug against Schistosoma-Associated Bladder Cancer Targeting Protein Signaling: Computational Drug Repositioning Approach.","volume":"57","author":"AJ Siddiqui","year":"2021","journal-title":"Medicina"},{"issue":"1","key":"pntd.0012453.ref084","article-title":"Molecular modeling and design of some \u03b2-amino alcohol grafted 1, 4, 5-trisubstituted 1, 2, 3-triazoles derivatives against chloroquine sensitive, 3D7 strain of Plasmodium falciparum.","volume":"7","author":"ZYu Ibrahim","year":"2021","journal-title":"Heliyon"},{"key":"pntd.0012453.ref085","first-page":"1","article-title":"You must be flexible enough to be trained, Mr. Dynamics simulator.","author":"AU Danazumi","year":"2023","journal-title":"Molecular Diversity"},{"key":"pntd.0012453.ref086","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.addr.2016.05.007","article-title":"BDDCS, the Rule of 5 and drugability","volume":"101","author":"LZ Benet","year":"2016","journal-title":"Adv Drug Deliv Rev"},{"issue":"1","key":"pntd.0012453.ref087","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1080\/2314808X.2022.2050115","article-title":"Molecular Docking, ADMET and Pharmacokinetic properties predictions of some di-aryl Pyridinamine derivatives as Estrogen Receptor (Er+) Kinase Inhibitors.","volume":"9","author":"SH Abdullahi","year":"2022","journal-title":"Egyptian Journal of Basic and Applied Sciences"},{"issue":"3","key":"pntd.0012453.ref088","first-page":"94","article-title":"The Central Role of Cytochrome P450","volume":"11","author":"F Esteves","year":"2021","journal-title":"Xenobiotic Metabolism-A Brief Review on a Fascinating Enzyme Family. Journal of xenobiotics"},{"issue":"10","key":"pntd.0012453.ref089","doi-asserted-by":"crossref","first-page":"6045","DOI":"10.3390\/app13106045","article-title":"Impact of Cytochrome P450 Enzymes on the Phase I Metabolism of Drugs.","volume":"13","author":"D Iacopetta","year":"2023","journal-title":"Applied Sciences"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T17:24:10Z","timestamp":1726161850000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012453"}},"subtitle":[],"editor":[{"given":"David Joseph","family":"Diemert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,9,12]]},"references-count":89,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0012453","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,12]]}}}