{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:19:49Z","timestamp":1790957989318,"version":"4.1.0"},"reference-count":179,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aedes aegypti is the main vector that transmits viral diseases such as dengue, hemorrhagic dengue, urban yellow fever, zika, and chikungunya. Worldwide, many cases of dengue have been reported in recent years, showing significant growth. The best way to manage diseases transmitted by Aedes aegypti is to control the vector with insecticides, which have already been shown to be toxic to humans; moreover, insects have developed resistance. Thus, the development of new insecticides is considered an emergency. One way to achieve this goal is to apply computational methods based on ligands and target information. In this study, sixteen compounds with acceptable insecticidal activities, with 100% larvicidal activity at low concentrations (2.0 to 0.001 mg\u00b7L\u22121), were selected from the literature. These compounds were used to build up and validate pharmacophore models. Pharmacophore model 6 (AUC = 0.78; BEDROC = 0.6) was used to filter 4793 compounds from the subset of lead-like compounds from the ZINC database; 4142 compounds (dG &lt; 0 kcal\/mol) were then aligned to the active site of the juvenile hormone receptor Aedes aegypti (PDB: 5V13), 2240 compounds (LE &lt; \u22120.40 kcal\/mol) were prioritized for molecular docking from the construction of a chitin deacetylase model of Aedes aegypti by the homology modeling of the Bombyx mori species (PDB: 5ZNT), which aligned 1959 compounds (dG &lt; 0 kcal\/mol), and 20 compounds (LE &lt; \u22120.4 kcal\/mol) were predicted for pharmacokinetic and toxicological prediction in silico (Preadmet, SwissADMET, and eMolTox programs). Finally, the theoretical routes of compounds M01, M02, M03, M04, and M05 were proposed. Compounds M01\u2013M05 were selected, showing significant differences in pharmacokinetic and toxicological parameters in relation to positive controls and interaction with catalytic residues among key protein sites reported in the literature. For this reason, the molecules investigated here are dual inhibitors of the enzymes chitin synthase and juvenile hormonal protein from insects and humans, characterizing them as potential insecticides against the Aedes aegypti mosquito.<\/jats:p>","DOI":"10.3390\/ijms23158218","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T22:03:42Z","timestamp":1658873022000},"page":"8218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of Potential Insect Growth Inhibitor against Aedes aegypti: A Bioinformatics Approach"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4182-376X","authenticated-orcid":false,"given":"Glauber V.","family":"Da Costa","sequence":"first","affiliation":[{"name":"Graduate Program in Network in Pharmaceutical Innovation, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"},{"name":"Laboratory of Biotechnology in Natural Products, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moys\u00e9s F. A.","family":"Neto","sequence":"additional","affiliation":[{"name":"Laboratory Molecular Modeling, State University of Feira de Santana, Feira de Santana 44036-900, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia K. P.","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology in Natural Products, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester M. F.","family":"De S\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology in Natural Products, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luanne C. F.","family":"Cancela","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology in Natural Products, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanina S.","family":"Vega","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology in Natural Products, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1ssio M.","family":"Lobato","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"},{"name":"Laboratory of Biotechnology in Natural Products, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9221-7749","authenticated-orcid":false,"given":"Juliana P.","family":"Zuliani","sequence":"additional","affiliation":[{"name":"Laboratory Cellular Immunology Applied to Health, Oswaldo Cruz Foundation, FIOCRUZ Rond\u00f4nia, Porto Velho 78912-000, RO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-1095","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Espejo-Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Institute of Biosanitary Research ibs, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-8123","authenticated-orcid":false,"given":"Joaqu\u00edn M.","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Institute of Biosanitary Research ibs, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco H. A.","family":"Leite","sequence":"additional","affiliation":[{"name":"Laboratory Molecular Modeling, State University of Feira de Santana, Feira de Santana 44036-900, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0271-335X","authenticated-orcid":false,"given":"Cleydson B. R.","family":"Santos","sequence":"additional","affiliation":[{"name":"Graduate Program in Network in Pharmaceutical Innovation, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, Macap\u00e1 68902-280, AP, Brazil"},{"name":"Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Institute of Biosanitary Research ibs, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Georghiou, G.P., and Saito, T. (1983). Pest Resistance to Pesticides, Springer Science & Business Media.","DOI":"10.1007\/978-1-4684-4466-7"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1586\/14760584.4.4.553","article-title":"Yellow Fever Vaccine","volume":"4","author":"Monath","year":"2005","journal-title":"Expert Rev. Vaccines"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1023\/A:1012901832162","article-title":"Insect Growth Regulators and Their Potential in the Management of Stored-Product Insect Pests","volume":"5","author":"Mondal","year":"2000","journal-title":"Integr. Pest Manag. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gilbert, L.I. (1976). The Juvenile Hormones, Springer US. PLENUM PRE.","DOI":"10.1007\/978-1-4684-7947-8"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/0020-1790(81)90083-4","article-title":"The Distribution of Juvenile Hormone Esterase and Its Interrelationship with Other Proteins Influencing Juvenile Hormone Metabolism in the Cabbage Looper, Trichoplusia Ni","volume":"11","author":"Wing","year":"1981","journal-title":"Insect Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/BF02981447","article-title":"Recent Advances in Hormones in Insect Pest Control","volume":"26","author":"Hoffmann","year":"1998","journal-title":"Phytoparasitica"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.ibmb.2004.03.021","article-title":"Nutritional Regulation of JH Synthesis: A Mechanism to Control Reproductive Maturation in Mosquitoes?","volume":"34","author":"Noriega","year":"2004","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/0022-1910(75)90234-6","article-title":"Stiffness and Tanning of Sclerites","volume":"21","author":"Hepburn","year":"1975","journal-title":"J. Insect Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0020-1790(88)90070-4","article-title":"Chitin Synthesis in Insect Cell Lines","volume":"18","author":"Londershausen","year":"1988","journal-title":"Insect Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/0020-1790(86)90059-4","article-title":"Insect Chitin. Physical State, Synthesis, Degradation and Metabolic Regulation","volume":"16","author":"Kramer","year":"1986","journal-title":"Insect Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ibmb.2009.10.007","article-title":"Insect Cuticular Sclerotization: A Review","volume":"40","author":"Andersen","year":"2010","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00360-005-0005-3","article-title":"Insect Chitin Synthases: A Review","volume":"176","author":"Merzendorfer","year":"2006","journal-title":"J. Comp. Physiol. B Biochem. Syst. Environ. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Doucet, D., and Retnakaran, A. (2012). Insect Chitin. Metabolism, Genomics and Pest Management, Elsevier Ltd.. [1st ed.].","DOI":"10.1016\/B978-0-12-391500-9.00006-1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/07391102.2020.1808074","article-title":"Identification of Novel Aedes Aegypti Odorant-Binding Protein 1 Modulators by Ligand and Structure-Based Approaches and Bioassays","volume":"40","author":"Neto","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s10822-006-9070-2","article-title":"A Marriage Made in Torsional Space: Using GALAHAD Models to Drive Pharmacophore Multiplet Searches","volume":"20","author":"Shepphird","year":"2006","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1002\/qsar.200730163","article-title":"3D-QSAR Studies on a Class of IKK-2 Inhibitors with GALAHAD Used to Develop Molecular Alignment Models","volume":"27","author":"Long","year":"2008","journal-title":"QSAR Comb. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.ejmech.2017.03.043","article-title":"An Integrated Approach towards the Discovery of Novel Non-Nucleoside Leishmania Major Pteridine Reductase 1 Inhibitors","volume":"132","author":"Leite","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e427","DOI":"10.1016\/j.ddtec.2013.02.001","article-title":"Multi-Objective Optimization Methods in Drug Design","volume":"10","author":"Nicolaou","year":"2013","journal-title":"Drug Discov. Today Technol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bittencourt, J.A.H.M., Neto, M.F.A., Lacerda, P.S., Bittencourt, R.C.V.S., Silva, R.C., Lobato, C.C., Silva, L.B., Leite, F.H.A., Zuliani, J.P., and Rosa, J.M.C. (2019). In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity. Molecules, 24.","DOI":"10.3390\/molecules24081476"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhao, W., Hevener, K.E., White, S.W., Lee, R.E., and Boyett, J.M. (2009). A Statistical Framework to Evaluate Virtual Screening. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-10-225"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1021\/ci600426e","article-title":"Evaluating Virtual Screening Methods: Good and Bad Metrics for the \u201cEarly Recognition\u201d Problem","volume":"47","author":"Truchon","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13321-016-0167-x","article-title":"Benchmark of Four Popular Virtual Screening Programs: Construction of the Active\/Decoy Dataset Remains a Major Determinant of Measured Performance","volume":"8","author":"Chaput","year":"2016","journal-title":"J. Cheminform."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1080\/07391102.2020.1796791","article-title":"Pharmacophore-Based Virtual Screening and Molecular Docking to Identify Promising Dual Inhibitors of Human Acetylcholinesterase and Butyrylcholinesterase","volume":"39","author":"Mascarenhas","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev.biophys.32.110601.142532","article-title":"Molecular Recognition and Docking Algorithms","volume":"32","author":"Brooijmans","year":"2003","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5912","DOI":"10.1021\/jm050362n","article-title":"A Critical Assessment of Docking Programs and Scoring Functions","volume":"49","author":"Warren","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.drudis.2010.03.013","article-title":"Pharmacophore Modeling and Applications in Drug Discovery: Challenges and Recent Advances","volume":"15","author":"Yang","year":"2010","journal-title":"Drug Discov. Today"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12899","DOI":"10.1039\/c0cp00151a","article-title":"Scoring Functions and Their Evaluation Methods for Protein-Ligand Docking: Recent Advances and Future Directions","volume":"12","author":"Huang","year":"2010","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0008-6215(99)00190-1","article-title":"Van Der Chemical Synthesis of N-Acetylglucosamine Derivatives and Their Use as Glycosyl Acceptors by the Mesorhizobium Loti Chitin Oligosaccharide Synthase NodC","volume":"321","author":"Kamst","year":"1999","journal-title":"Carbohydr. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1007\/s00044-012-0177-9","article-title":"CHEMISTRY Pharmacophore-Based 3D-QSAR Study of Fungal Chitin Synthase Inhibitors","volume":"22","author":"Rohidas","year":"2013","journal-title":"Med. Chem. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liszekova, D., Polakovic, M., Ben, M., and Farkas, R. (2009). Molecular Determinants of Juvenile Hormone Action as Revealed by 3D QSAR Analysis in Drosophila. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006001"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5948","DOI":"10.1007\/s00044-013-0585-5","article-title":"CHEMISTRY 3D-QSAR Studies on the Biological Activity of Juvenile Hormone Mimetic Compounds for Culex Pipiens Larvae","volume":"22","author":"Latha","year":"2013","journal-title":"Med. Chem. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1016\/j.bmcl.2010.04.144","article-title":"Synthesis, Larvicidal Activity, and SAR Studies of New Benzoylphenylureas Containing Oxime Ether and Oxime Ester Group","volume":"20","author":"Sun","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"ZINC\u2014A Free Database of Commercially Available Compounds for Virtual Screening","volume":"45","author":"Irwin","year":"2005","journal-title":"J. Chem. Inf. Model."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1021\/acs.jcim.5b00559","article-title":"ZINC 15\u2014Ligand Discovery for Everyone","volume":"55","author":"Sterling","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kralj, S., Juki\u010d, M., and Bren, U. (2022). Commercial SARS-CoV-2 Targeted, Protease Inhibitor Focused and Protein\u2013Protein Interaction Inhibitor Focused Molecular Libraries for Virtual Screening and Drug Design. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010393"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kolari\u010d, A., Juki\u010d, M., and Bren, U. (2022). Novel Small-Molecule Inhibitors of the SARS-CoV-2 Spike Protein Binding to Neuropilin 1. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020165"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Da Costa, G.V., Ferreira, E.F.B., de Ramos, R.S., Da Silva, L.B., De S\u00e1, E.M.F., Da Silva, A.K.P., Lobato, C.M., Souto, R.N.P., da Silva de P, C.H.T., and Federico, L.B. (2019). Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos. Pharmaceuticals, 12.","DOI":"10.3390\/ph12020061"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Juki\u010d, M., Jane\u017ei\u010d, D., and Bren, U. (2020). Ensemble Docking Coupled to Linear Interaction Energy Calculations for Identification of Coronavirus Main Protease (3CLpro) Non-Covalent Small-Molecule Inhibitors. Molecules, 25.","DOI":"10.3390\/molecules25245808"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pinto, V.d.S., Ara\u00fajo, J.S.C., Silva, R.C., da Costa, G.V., Cruz, J.N., Neto, M.F.D.A., Campos, J.M., Santos, C.B.R., Leite, F.H.A., and Junior, M.C.S. (2019). In Silico Study to Identify New Antituberculosis Molecules from Natural Sources by Hierarchical Virtual Screening and Molecular Dynamics Simulations. Pharmaceuticals, 12.","DOI":"10.3390\/ph12010036"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jmgm.2013.01.010","article-title":"Pharmacophore Modeling, Virtual Screening, Docking and in Silico ADMET Analysis of Protein Kinase B (PKB \u03b2) Inhibitors","volume":"42","author":"Vyas","year":"2013","journal-title":"J. Mol. Graph. Model."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1074\/jbc.RA119.007597","article-title":"Structural and Biochemical Insights into the Catalytic Mechanisms of Two Insect Chitin Deacetylases of the Carbohydrate Esterase 4 Family","volume":"294","author":"Liu","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9416","DOI":"10.1021\/bi0606694","article-title":"Structure and Mechanism of Chitin Deacetylase from the Fungal Pathogen Colletotrichum Lindemuthianum","volume":"45","author":"Blair","year":"2006","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1126\/science.1138878","article-title":"Genome Sequence of Aedes Aegypti, a Major Arbovirus Vector","volume":"316","author":"Nene","year":"2007","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fimmu.2020.01828","article-title":"NLRP3 Sensing of Diverse Inflammatory Stimuli Requires Distinct Structural Features","volume":"11","author":"Rahman","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_45","first-page":"10","article-title":"Comparative Structure Analysis of Tyramine- \u03b2 -Hydroxylase from Fruit Fly and ADME\/T-Based Profiling of 1-Arylimidazole-2 (3 H) -Thiones as Potential Inhibitors","volume":"4","author":"Hasan","year":"2016","journal-title":"Int. J. Anal. Bio-Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1107\/S090744491301158X","article-title":"Half a Century of Ramachandran Plots","volume":"69","author":"Carugo","year":"2013","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1002\/pro.128","article-title":"Structural and Functional Characterization of a Putative Polysaccharide Deacetylase of the Human Parasite Encephalitozoon Cuniculi","volume":"18","author":"Urch","year":"2009","journal-title":"Protein Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"31126","DOI":"10.1074\/jbc.M112.390005","article-title":"The Structure- and Metal-Dependent Activity of Escherichia Coli PgaB Provides Insight into the Partial De-N-Acetylation of Poly-\u03b2-1,6-N-Acetyl-d-Glucosamine","volume":"287","author":"Little","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6882","DOI":"10.1002\/anie.201400220","article-title":"Structural Basis of Chitin Oligosaccharide Deacetylation","volume":"53","author":"Moerschbacher","year":"2014","journal-title":"Angew. Chem.-Int. Ed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1128\/JB.00838-08","article-title":"Streptococcus Mutans SMU.623c Codes for a Functional, Metal-Dependent Polysaccharide Deacetylase That Modulates Interactions with Salivary Agglutinin","volume":"91","author":"Dong","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10968","DOI":"10.1074\/jbc.M513066200","article-title":"Structure and Activity of Two Metal Ion-Dependent Acetylxylan Esterases Involved in Plant Cell Wall Degradation Reveals a Close Similarity to Peptidoglycan Deacetylases","volume":"281","author":"Taylor","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1023\/A:1007934310264","article-title":"A Comparison of Heuristic Search Algorithms for Molecular Docking","volume":"11","author":"Westhead","year":"1997","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1023\/A:1007996124545","article-title":"Empirical Scoring Functions: I. The Development of a Fast Empirical Scoring Function to Estimate the Binding Affinity of Ligands in Receptor Complexes","volume":"11","author":"Eldridge","year":"1997","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","article-title":"Automated Docking Using a Lamarckian Genetic Algorithm and an Empirical Binding Free Energy Function","volume":"19","author":"Morris","year":"1998","journal-title":"J. Comput. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1021\/acs.jcim.9b00778","article-title":"Autodock Vina Adopts More Accurate Binding Poses but Autodock4 Forms Better Binding Affinity","volume":"60","author":"Nguyen","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13062-020-00267-2","article-title":"AMDock: A Versatile Graphical Tool for Assisting Molecular Docking with Autodock Vina and Autodock4","volume":"15","author":"Valiente","year":"2020","journal-title":"Biol. Direct"},{"key":"ref_57","first-page":"3378","article-title":"Identification of Novel Antiplasmodial Compound by Hierarquical Virtual Screening and in Vitro Assays","volume":"39","author":"Neri","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nrd4163","article-title":"The Role of Ligand Efficiency Metrics in Drug Discovery","volume":"13","author":"Hopkins","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1080\/14756360802166665","article-title":"CoMFA and CoMSIA 3D-QSAR Analysis on Hydroxamic Acid Derivatives as Urease Inhibitors","volume":"24","author":"Wadood","year":"2009","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1021\/ci800084x","article-title":"An Alternative Method for the Evaluation of Docking Performance: RSR vs RMSD","volume":"48","author":"Yusuf","year":"2008","journal-title":"J. Chem. Inf. Model."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1021\/acs.jcim.8b00981","article-title":"Discovery of Novel Potential Human Targets of Resveratrol by Inverse Molecular Docking","volume":"59","author":"Kores","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Furlan, V., and Bren, U. (2021). Insight into Inhibitory Mechanism of Pde4d by Dietary Polyphenols Using Molecular Dynamics Simulations and Free Energy Calculations. Biomolecules, 11.","DOI":"10.3390\/biom11030479"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Le\u0161nik, S., and Bren, U. (2022). Mechanistic Insights into Biological Activities of Polyphenolic Compounds from Rosemary Obtained by Inverse Molecular Docking. Foods, 11.","DOI":"10.3390\/foods11010067"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13321-019-0330-2","article-title":"The Nature of Ligand Efficiency","volume":"11","author":"Kenny","year":"2019","journal-title":"J. Cheminform."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15329","DOI":"10.1074\/jbc.M117.802009","article-title":"A Mosquito Hemolymph Odorant-Binding Protein Family Member Specifically Binds Juvenile Hormone","volume":"292","author":"Kim","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/82644","article-title":"MAML1, a Human Homologue of Drosophila Mastermind, Is a Transcriptional Co-Activator for NOTCH Receptors","volume":"26","author":"Wu","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00894-017-3548-9","article-title":"Similarity Search Combined with Docking and Molecular Dynamics for Novel HAChE Inhibitor Scaffolds","volume":"24","author":"Borges","year":"2018","journal-title":"J. Mol. Model."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lobato Rodrigues, A.B., Martins, R.L., Rabelo, \u00c9.D.M., Tomazi, R., Santos, L.L., Brand\u00e3o, L.B., Faustino, C.G., Ferreira Farias, A.L., Dos Santos, C.B.R., and de Castro Cantu\u00e1ria, P. (2021). Development of nano-emulsions based on Ayapana triplinervis essential oil for the control of Aedes aegypti larvae. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0254225"},{"key":"ref_69","first-page":"18","article-title":"Molecular Docking Studies of Phytocompounds in Common Weeds with AChE Proteins of Aphids and Beetles","volume":"10","author":"Sinha","year":"2020","journal-title":"J. Biol. Act. Prod. Nat."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11356-014-3470-y","article-title":"Systemic Insecticides (Neonicotinoids and Fipronil): Trends, Uses, Mode of Action and Metabolites","volume":"22","author":"Belzunces","year":"2015","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ibmb.2018.10.005","article-title":"How Do Oral Insecticidal Compounds Cross the Insect Midgut Epithelium?","volume":"103","author":"Denecke","year":"2018","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_72","first-page":"627","article-title":"Active Control of the Mechancal Ixsect Endocuticle Properties","volume":"8","year":"1967","journal-title":"Ins. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/0020-1790(75)90030-X","article-title":"An in vitro system for the quantitative measurement of CHITIN synthesis in the cockroach: Inhibition by TH 6040 and polyoxin D","volume":"5","author":"Sowa","year":"1975","journal-title":"Insect Biochem."},{"key":"ref_74","first-page":"237","article-title":"Benzoylphenyl Ureas\u2014A New Group of Larvicides Interfering with Chitin Deposition","volume":"19111","author":"Verloop","year":"1977","journal-title":"Am. Chem. Soc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1021\/jf00079a045","article-title":"Radiosynthesis of [Benzoyl-3,4,5-3H] diflubenzuron by a Route Applicable to Other High-Potency Insect Growth Regulators","volume":"36","author":"Tecle","year":"1988","journal-title":"J. Agric. Food Chem."},{"key":"ref_76","first-page":"326","article-title":"An Overview of the Main Pathways of Metabolic Resistance in Insects","volume":"13","author":"Panini","year":"2016","journal-title":"Invertebr. Surviv. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.pestbp.2014.11.014","article-title":"IRAC: Mode of Action Classification and Insecticide Resistance Management","volume":"121","author":"Sparks","year":"2015","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/cmdc.201600182","article-title":"A BOILED-Egg to Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules","volume":"11","author":"Daina","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_79","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":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1021\/jm901241e","article-title":"Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success","volume":"52","author":"Lovering","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1021\/ci034243x","article-title":"ESOL: Estimating Aqueous Solubility Directly from Molecular Structure","volume":"44","author":"Delaney","year":"2004","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1021\/ci200387c","article-title":"Revisiting the General Solubility Equation: In Silico Prediction of Aqueous Solubility Incorporating the Effect of Topographical Polar Surface Area","volume":"52","author":"Ali","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1021\/js9803205","article-title":"MDCK (Madin-Darby Canine Kidney) Cells: A Tool for Membrane Permeability Screening","volume":"88","author":"Irvine","year":"1999","journal-title":"J. Pharm. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2133\/dmpk.19.327","article-title":"In Silico Approaches for Predicting ADME Properties of Drugs","volume":"19","author":"Yamashita","year":"2004","journal-title":"Drug Metab Pharm."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/j.1745-7254.2005.00068.x","article-title":"Predictive Model of Blood-Brain Barrier Penetration of Organic Compounds","volume":"26","author":"Ma","year":"2005","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.tet.2009.11.002","article-title":"Toward Molecular Design for Hazard Reduction-Fundamental Relationships between Chemical Properties and Toxicity","volume":"66","author":"Voutchkova","year":"2010","journal-title":"Tetrahedron"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1124\/jpet.112.193433","article-title":"P-Glycoprotein Is a Major Determinant of Norbuprenorphine Brain Exposure and Antinociception","volume":"343","author":"Regina","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1021\/jm00253a001","article-title":"Quantitative Structure-Activity Relation of Reversible Dihydrofolate Reductase Inhibitors. Diaminotriazines","volume":"17","author":"Hansch","year":"1974","journal-title":"J. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1007\/s13738-020-01902-5","article-title":"QSAR Modeling, Molecular Docking and ADMET\/Pharmacokinetic Studies: A Chemometrics Approach to Search for Novel Inhibitors of Norepinephrine Transporter as Potent Antipsychotic Drugs","volume":"17","author":"Babatunde","year":"2020","journal-title":"J. Iran. Chem. Soc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"127930","DOI":"10.1016\/j.bmcl.2021.127930","article-title":"Development of an a Priori Computational Approach for Brain Uptake of Compounds in an Insect Model System","volume":"40","author":"Geldenhuys","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.drudis.2007.12.010","article-title":"The Role of ABC Transporters in Drug Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME-Tox)","volume":"13","author":"Sarkadi","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5388","DOI":"10.1016\/j.bmc.2012.03.045","article-title":"Fingerprint-Based in Silico Models for the Prediction of P-Glycoprotein Substrates and Inhibitors","volume":"20","author":"Poongavanam","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.addr.2015.03.001","article-title":"Prediction of Drug-ABC-Transporter Interaction-Recent Advances and Future Challenges","volume":"86","author":"Montanari","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1111\/imb.12052","article-title":"Silencing of P-Glycoprotein Increases Mortality in Temephos-Treated Aedes Aegypti Larvae","volume":"22","author":"Mansur","year":"2013","journal-title":"Insect Mol. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Yava\u015foglu, S.\u0130., Alkhaibari, A.M., and \u015eim\u015fek, F.M. (2022). Investigation of the insecticide resistance levels and mechanisms of the Mediterranean and Aegean Aedes caspius populations of Turkey. Int. J. Pest Manag.","DOI":"10.1080\/09670874.2022.2083263"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1365-2915.2008.00712.x","article-title":"Defence Mechanisms against Insecticides Temephos and Diflubenzuron in the Mosquito Aedes Caspius: The P-Glycoprotein Efflux Pumps","volume":"22","author":"Porretta","year":"2008","journal-title":"Med. Vet. Entomol."},{"key":"ref_97","first-page":"964","article-title":"Evaluation of the Role of ATP-Binding Cassette Transporters as a Defense Mechanism against Temephos in Populations of Aedes Aegypti","volume":"109","author":"Lima","year":"2014","journal-title":"Mem. Do Inst. Oswaldo Cruz"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Merzendorfer, H. (2014). ABC Transporters and Their Role in Protecting Insects from Pesticides and Their Metabolites, Elsevier Inc.. [1st ed.].","DOI":"10.1016\/B978-0-12-417010-0.00001-X"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1002\/ps.4935","article-title":"Predicting Mammalian Metabolism and Toxicity of Pesticides in Silico","volume":"74","author":"Clark","year":"2018","journal-title":"Pest Manag. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1093\/bioinformatics\/bty135","article-title":"EMolTox: Prediction of Molecular Toxicity with Confidence","volume":"34","author":"Ji","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"23","DOI":"10.22270\/jddt.v9i6.3653","article-title":"In Silico Toxicological, Anti-Tubercular Effect Evaluation And In Vitro Marine Pathogenic Bacteria Inhibition of N-[(3-Chloro-4-Nitro-Phenyl)Methyleneamino]Pyridine-4-Carboxamidine","volume":"9","author":"Mokhnache","year":"2019","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13321-020-00422-x","article-title":"KnowTox: Pipeline and Case Study for Confident Prediction of Potential Toxic Effects of Compounds in Early Phases of Development","volume":"12","author":"Morger","year":"2020","journal-title":"J. Cheminform."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Mokhnache, K., Karbab, A., Soltani, E.K., Bououden, W., Ouhida, S., Arrar, L., Esteban, M.A., Charef, N., and Mubarak, M.S. (2020). Synthesis, Characterization, Toxic Substructure Prediction, Hepatotoxicity Evaluation, Marine Pathogenic Bacteria Inhibition, and DFT Calculations of a New Hydrazone Derived from Isoniazid. J. Mol. Struct., 1221.","DOI":"10.1016\/j.molstruc.2020.128817"},{"key":"ref_104","first-page":"e2020016","article-title":"Assessment of the Cytotoxic and Mutagenic Potential of Dichlorvos (DDVP) Using in Silico Classification Model; a Health Hazard Awareness in Nigeria","volume":"35","author":"Abaukaka","year":"2020","journal-title":"Environ. Health Toxicol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1021\/acs.jcim.8b00685","article-title":"Comparative Study of Multitask Toxicity Modeling on a Broad Chemical Space","volume":"59","author":"Sosnin","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"ref_106","first-page":"2020","article-title":"In Silico Toxicity Prediction Using an Integrative Multimodel Approach","volume":"5","author":"Hernandez","year":"2020","journal-title":"Res. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"111663","DOI":"10.1016\/j.fct.2020.111663","article-title":"The Integrated Use of in Silico Methods for the Hepatotoxicity Potential of Piper Methysticum","volume":"145","author":"Tugcu","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1039\/C9AY02582K","article-title":"Identification, Isolation, Structural Characterisation, Synthesis and: In Silico Toxicity Prediction of the Alkaline Hydrolytic Degradation Product of Brivaracetam by Using LC-PDA, Preparative HPLC, LC\/HESI\/LTQ, FTIR, and 1H NMR","volume":"12","author":"Bhamare","year":"2020","journal-title":"Anal. Methods"},{"key":"ref_109","first-page":"915","article-title":"Evaluation of Pyocyanin Induced Systemic Pathogenicity of Pseudomonas Aeruginosa","volume":"33","author":"Rashid","year":"2020","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s10822-020-00310-4","article-title":"Revealing Cytotoxic Substructures in Molecules Using Deep Learning","volume":"34","author":"Webel","year":"2020","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2362.33.s2.5.x","article-title":"Organic Anion-Transporting Polypeptide (OATP) Transporter Family and Drug Disposition","volume":"33","author":"Kim","year":"2003","journal-title":"Eur. J. Clin. Investig. Suppl."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1517\/phgs.5.3.273.29831","article-title":"Pharmacogenomics of the OATP and OAT Families","volume":"5","author":"Marzolini","year":"2004","journal-title":"Pharmacogenomics"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1517\/17425255.1.3.429","article-title":"Role of the Liver-Specific Transporters OATP1B1 and OATP1B3 in Governing Drug Elimination","volume":"1","author":"Smith","year":"2005","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1021\/acs.molpharmaceut.5b00763","article-title":"Downregulation of Organic Anion Transporting Polypeptide (OATP) 1B1 Transport Function by Lysosomotropic Drug Chloroquine: Implication in OATP-Mediated Drug-Drug Interactions","volume":"13","author":"Alam","year":"2016","journal-title":"Mol. Pharmaceut."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1172\/JCI59526","article-title":"Complete OATP1B1 and OATP1B3 Deficiency Causes Human Rotor Syndrome by Interrupting Conjugated Bilirubin Reuptake into the Liver","volume":"122","author":"Wagenaar","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1021\/ci400395c","article-title":"How Does Catalase Release Nitric Oxide? A Computational Structure-Activity Relationship Study","volume":"53","author":"Vankayala","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1080\/14756366.2018.1490733","article-title":"Inhibition of \u03b1-, \u03b2-, \u03b3-, and \u03b4-Carbonic Anhydrases from Bacteria and Diatoms with N\u2032-Aryl-N-Hydroxy-Ureas","volume":"33","author":"Berrino","year":"2018","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/(SICI)1099-1263(1998090)18:5<301::AID-JAT503>3.0.CO;2-G","article-title":"Genotoxicity Evaluation of Buprofezin, Petroleum Oil and Profenofos in Somatic and Germ Cells of Male Mice","volume":"18","author":"Fahmy","year":"1998","journal-title":"J. Appl. Toxicol."},{"key":"ref_119","unstructured":"Booth, D.F.M. (1977). Pesticides in Aquatic Environments. Environmental Science Research, Springer Science & Business Media."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"6847","DOI":"10.1021\/acs.jafc.5b02460","article-title":"Benzoylurea Chitin Synthesis Inhibitors","volume":"63","author":"Sun","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.chemosphere.2017.05.009","article-title":"The Tissue Distribution, Metabolism and Hepatotoxicity of Benzoylurea Pesticides in Male Eremias Argus after a Single Oral Administration","volume":"183","author":"Chang","year":"2017","journal-title":"Chemosphere"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1021\/tx1000865","article-title":"Developing Structure-Activity Relationships for the Prediction of Hepatotoxicity","volume":"23","author":"Greene","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"362","DOI":"10.3389\/fchem.2018.00362","article-title":"Prediction Is a Balancing Act: Importance of Sampling Methods to Balance Sensitivity and Specificity of Predictive Models Based on Imbalanced Chemical Data Sets","volume":"6","author":"Banerjee","year":"2018","journal-title":"Front. Chem."},{"key":"ref_124","unstructured":"de Knecht, J.A., and van Herwijnen, R. (2008). Environmental Risk Limits for Deltamethrin, RIVM Letter report 601716015\/2008; National Institute for Public Health and the Environment."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.aquatox.2015.07.008","article-title":"Transcriptional Responses to Teflubenzuron Exposure in European Lobster (Homarus Gammarus)","volume":"167","author":"Olsvik","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.aquatox.2014.01.019","article-title":"Mortality and Deformities in European Lobster (Homarus Gammarus) Juveniles Exposed to the Anti-Parasitic Drug Teflubenzuron","volume":"149","author":"Samuelsen","year":"2014","journal-title":"Aquat. Toxicol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1096\/fj.06-6730hyp","article-title":"Defining a Binding Pocket for Sulfonylureas in ATP-sensitive Potassium Channels","volume":"21","author":"Zhao","year":"2007","journal-title":"FASEB J."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/jee\/73.4.520","article-title":"Effect of 3 New Moult-Inhibiting Insect Growth Regulators on the Spruce Budworm1","volume":"73","author":"Retnakaran","year":"1980","journal-title":"J. Econ. Entomol."},{"key":"ref_129","first-page":"291","article-title":"V Inhibition of DNA Synthesis by Hydroxyureas and Related Compounds: Structure-Activity Relationships","volume":"24","author":"Mandloi","year":"2001","journal-title":"Oxid. Commun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1021\/ja012075o","article-title":"Binding of Hydrophobic Hydroxamic Acids Enhances Peroxidase\u2019s Stereoselectivity in Nonaqueous Sulfoxidations","volume":"124","author":"Das","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1248\/cpb.50.1280","article-title":"N-Substituted Hydroxyureas as Urease Inhibitors","volume":"50","author":"Uesato","year":"2002","journal-title":"Chem. Pharm. Bull."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"13392","DOI":"10.1021\/jp0505429","article-title":"Quantum Chemical Design of Hydroxyurea Derivatives for the Treatment of Sickle-Cell Anemia","volume":"109","author":"Rohrman","year":"2005","journal-title":"J. Phys. Chem. B"},{"key":"ref_133","first-page":"14","article-title":"(12) United States Patent Date of Patent","volume":"1","author":"Ryan","year":"2009","journal-title":"Syst. Method Program. A Weigh. Scale Usinga Key Signal Enter A Program. Mode"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"580","DOI":"10.2174\/157018011796235257","article-title":"Computational Analysis of the Apoptotic Activity of a Small Library of Novel Substituted Hydroxy Ureas Designed as Potential Inhibitors of Ribonucleotide Reductase","volume":"8","author":"McCourt","year":"2011","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0065-2571(81)90014-5","article-title":"Regulation of Ribonucleotide Reductase in Mammalian Cells by Chemotherapeutic Agents","volume":"19","author":"Elford","year":"1981","journal-title":"Adv. Enzym. Regul."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0166-6851(86)90005-8","article-title":"P-Alkyloxybenz Hydroxamic Acids, Effective Inhibitors of the trypanosome Glycerol-3-Phosphate Oxidase","volume":"19","author":"Grady","year":"1986","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_137","first-page":"179","article-title":"Quantitative Structure-Activity Relationship Study on Some 5-Lipoxygenase Inhibitors","volume":"3","author":"Gupta","year":"1990","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1021\/jm00165a017","article-title":"Hydroxamic Acid Inhibitors of 5-Lipoxygenase: Quantitative Structure\u2013Activity Relationships","volume":"33","author":"Summers","year":"1990","journal-title":"J. Med. Chem."},{"key":"ref_139","first-page":"767","article-title":"A QSAR Study of the Effect of Benzohydroxamic Acids on DNA Synthesis","volume":"106","author":"Khadika","year":"1997","journal-title":"Bull. Des Soci\u00e9t\u00e9s Chim. Belg."},{"key":"ref_140","first-page":"17","article-title":"The Pattern Recognition Study on the Antitumor Activity of Aroyl Compounds","volume":"11","author":"Xuan","year":"2001","journal-title":"Chin. J. Med. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.bmcl.2006.11.053","article-title":"Inhibitors of the FEZ-1 Metallo-\u03b2-Lactamase","volume":"17","author":"Horsfall","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.comptc.2013.05.026","article-title":"Investigation of the Scavenging Mechanism of Tyrosyl Radical by Hydroxybenzohydroxamic Acid Derivatives: A DFT Study","volume":"1018","author":"Bayat","year":"2013","journal-title":"Comput. Theor. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s12272-018-1045-z","article-title":"Aspirin-Inspired Acetyl-Donating HDACs Inhibitors","volume":"41","author":"Lim","year":"2018","journal-title":"Arch. Pharmacal Res."},{"key":"ref_144","first-page":"2","article-title":"Synthesis and antibacterial activity of 2-acetyl and 2-formylpyrrole oximes, semicarbazones and phenylhydrazones","volume":"14","author":"Hania","year":"2002","journal-title":"Asian J. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Ramos, R.S., Borges, R.S., de Souza, J.S.N., Araujo, I.F., Chaves, M.H., and Santos, C.B.R. (2022). Identification of Potential Antiviral Inhibitors from Hydroxychloroquine and 1,2,4,5-Tetraoxanes Analogues and Investigation of the Mechanism of Action in SARS-CoV-2. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031781"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1021\/ci500568d","article-title":"Prediction of Synthetic Accessibility Based on Commercially Available Compound Databases","volume":"54","author":"Fukunishi","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41596-021-00659-2","article-title":"Artificial Intelligence\u2013Enabled Virtual Screening of Ultra-Large Chemical Libraries with Deep Docking","volume":"17","author":"Gentile","year":"2022","journal-title":"Nat. Protoc."},{"key":"ref_148","first-page":"65","article-title":"Preparation of Isoxazole-Pyridine Derivatives as GABA Modulators","volume":"4","author":"Buettelmann","year":"2010","journal-title":"PCT Int. Appl. WO"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"5264","DOI":"10.1021\/jacs.8b01618","article-title":"Scope and Mechanism of a True Organocatalytic Beckmann Rearrangement with a Boronic Acid\/Perfluoropinacol System under Ambient Conditions","volume":"140","author":"Mo","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1021\/acssynbio.6b00255","article-title":"Sen Engineering Iron Responses in Mammalian Cells by Signal-Induced Protein Proximity","volume":"6","author":"Zeng","year":"2017","journal-title":"ACS Synth. Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1039\/b802997k","article-title":"Efficient Stereoselective Nucleophilic Addition of Pyrroles to Chiral Nitrones","volume":"6","author":"Berini","year":"2008","journal-title":"Org. Biomol. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1016\/j.bmc.2016.08.066","article-title":"Synthesis and Bioactivity of Novel Isoxazole Chalcone Derivatives on Tyrosinase and Melanin Synthesis in Murine B16 Cells for the Treatment of Vitiligo","volume":"24","author":"Niu","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"5751","DOI":"10.1016\/j.tetlet.2014.08.083","article-title":"A Novel and Efficient Catalytic System Including TEMPO\/Acetaldoxime\/InCl3 for Aerobic Oxidation of Primary Amines to Oximes","volume":"55","author":"Yu","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nature23007","article-title":"Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway","volume":"547","author":"Viswanathan","year":"2017","journal-title":"Nature"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e29049","DOI":"10.1097\/MD.0000000000029049","article-title":"Design, synthesis, and biological evaluation of histone deacetylase inhibitor with novel salicylamide zinc binding group","volume":"101","author":"Kim","year":"2022","journal-title":"Medicine"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"40238","DOI":"10.1039\/C5RA25256C","article-title":"Benzoic Hydroxamate-Based Iron Complexes as Model Compounds for Humic Substances: Synthesis, Characterization and Algal Growth Experiments","volume":"6","author":"Orlowska","year":"2016","journal-title":"RSC Adv."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.1002\/ejoc.201900215","article-title":"Selective Room-Temperature Hydrogenation of Carbonyl Compounds under Atmospheric Pressure over Platinum Nanoparticles Supported on Ceria-Zirconia Mixed Oxide","volume":"2019","author":"Redina","year":"2019","journal-title":"Eur. J. Org. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/0020-1790(80)90090-6","article-title":"Characterization of A Chitin Synthase from the Stable Fly, Stomoxys Calcitrans (L.)","volume":"10","author":"Mayer","year":"1980","journal-title":"Insect Biochem."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/jcc.540100804","article-title":"Validation of the General Purpose Tripos 5.2 Force Field","volume":"10","author":"Clark","year":"1989","journal-title":"J. Comput. Chem."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1016\/0040-4020(80)80168-2","article-title":"Iterative Partial Equalization of Orbital Electronegativity-a Rapid Access to Atomic Charges","volume":"36","author":"Gasteiger","year":"1980","journal-title":"Tetrahedron"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s10822-006-9082-y","article-title":"GALAHAD: 1. Pharmacophore Identification by Hypermolecular Alignment of Ligands in 3D","volume":"20","author":"Richmond","year":"2006","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1021\/jm300687e","article-title":"Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking","volume":"55","author":"Mysinger","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13321-016-0158-y","article-title":"Rocker: Open Source, Easy-to-Use Tool for AUC and Enrichment Calculations and ROC Visualization","volume":"8","author":"Niinivehmas","year":"2016","journal-title":"J. Cheminform."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., and Madden, T.L. (2009). BLAST+: Architecture and Applications. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-10-421"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/elps.200900140","article-title":"Celebrating 30 Years Automated Comparative Protein Structure Modeling with SWISS-MODEL and Swiss-PdbViewer: A Historical Perspective","volume":"30","author":"Guex","year":"2009","journal-title":"Electrophoresis"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology Modelling of Protein Structures and Complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/nar\/gkw1132","article-title":"The SWISS-MODEL Repository\u2014New Features and Functionality","volume":"45","author":"Bienert","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1093\/bioinformatics\/btz828","article-title":"QMEANDisCo\u2013Distance Constraints Applied on Model Quality Estimation","volume":"36","author":"Studer","year":"2019","journal-title":"Struct. Bioinform."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/bioinformatics\/btq662","article-title":"Toward the Estimation of the Absolute Quality of Individual Protein Structure Models","volume":"27","author":"Benkert","year":"2011","journal-title":"Struct. Bioinform."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1093\/bioinformatics\/btg224","article-title":"Bioinformatics Applications note pisces: A Protein Sequence Culling Server","volume":"19","author":"Wang","year":"2003","journal-title":"Bioinformatics"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/prot.20497","article-title":"Comparing Protein-Ligand Docking Programs Is Difficult","volume":"60","author":"Cole","year":"2005","journal-title":"Proteins: Struct. Funct. Genet."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez, D., and Caballero, J. (2018). Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data?. Molecules, 23.","DOI":"10.3390\/molecules23051038"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Ramos, R.d.S., Costa, J.d.S., Mac\u00eado, W.J.d.C., Rodrigues, A.B.L., Silva, C., Santos, C., da Costa, G.V., Taft, C.A., Silva, R.C., and Souto, R.N.P. (2019). Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening. Pharmaceuticals, 12.","DOI":"10.3390\/ph12010020"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Le\u00e3o, R.P., Cruz, J.V., da Costa, G.V., Cruz, J.N., Ferreira, E.F.B., Silva, R.C., de Lima, L.R., Borges, R.S., Dos Santos, G.B., and Santos, C.B.R. (2020). Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach. Pharmaceuticals, 13.","DOI":"10.3390\/ph13090209"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Costa, R.A., Rocha, E.C.M., Silva, R.C., Gon\u00e7alves, A.S., Santos, C.B.R., and Brasil, D.S.B. (2022). A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B\/NS3 from Dengue Virus. Molecules, 27.","DOI":"10.3390\/molecules27134118"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s10822-006-9099-2","article-title":"Structure and Reaction Based Evaluation of Synthetic Accessibility","volume":"21","author":"Boda","year":"2007","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/minf.201200133","article-title":"Ambit-Tautomer: An Open Source Tool for Tautomer Generation","volume":"32","author":"Kochev","year":"2013","journal-title":"Mol. Inform."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1758-2946-1-8","article-title":"Estimation of Synthetic Accessibility Score of Drug-like Molecules Based on Molecular Complexity and Fragment Contributions","volume":"1","author":"Ertl","year":"2009","journal-title":"J. Cheminform."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13321-017-0203-5","article-title":"ExCAPE-DB: An Integrated Large Scale Dataset Facilitating Big Data Analysis in Chemogenomics","volume":"9","author":"Sun","year":"2017","journal-title":"J. Cheminform."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8218\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:56:41Z","timestamp":1760140601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,26]]},"references-count":179,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158218"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158218","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,26]]}}}