{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:51:11Z","timestamp":1775710271732,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>In malaria management, insecticides play a crucial role in targeting disease vectors. Benzothiazole derivatives have also been reported to possess insecticidal properties, among several other properties they exhibit. The female Anopheles mosquito is responsible for transmitting the malaria parasite when infected. <jats:italic>Anopheles gambiae<\/jats:italic> (<jats:italic>Ag<\/jats:italic>) and <jats:italic>Anopheles funestus<\/jats:italic> (<jats:italic>Af<\/jats:italic>) are two of the most notable Anopheles species known to spread malaria in Nigeria. Trehalase is an enzyme that breaks down trehalose. Recent research has proposed it as a viable target for inhibition since it aids in flight and stress adaptation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study aimed to investigate benzothiazole derivatives as potential inhibitors of trehalase of Anopheles funestus (<jats:italic>Af<\/jats:italic>Tre) and Anopheles gambiae (<jats:italic>Ag<\/jats:italic>Tre) using toxicity profiling, molecular docking, and dynamic simulation for future insecticidal intervention. A total of 4,214 benzothiazole-based compounds were obtained from the PubChem database and subjected to screening against the 3D modelled structure of <jats:italic>Af<\/jats:italic>Tre and <jats:italic>Ag<\/jats:italic>Tre. Compounds with some toxicity levels were optimised, and the obtained lead compounds were further investigated through molecular docking studies. Furthermore, the best hit was subjected to parameters such as RMSD, RMSF, SASA, Rg, and hydrogen bond to confirm its stability when in a complex with <jats:italic>Af<\/jats:italic>Tre, and these parameters were compared to that of validamycin A (control ligand).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>The post-screening analysis showed binding affinities of \u22128.7 and \u22128.2\u00a0kcal\/mol (compound 1), \u22128.2 and \u22127.4\u00a0kcal\/mol (compound 2), compared to \u22126.3 and \u22125.1\u00a0kcal\/mol (Validamycin A, a known inhibitor) against <jats:italic>Af<\/jats:italic>Tre and <jats:italic>Ag<\/jats:italic>Tre, respectively. The molecular dynamics simulation showed that compound 1 (the best hit) had good stability when in complex with <jats:italic>Af<\/jats:italic>Tre. These findings suggest that these best hits can serve as potential inhibitors for the development of novel insecticides in the control of malaria vectors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbinf.2024.1428539","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T05:13:25Z","timestamp":1723180405000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["In silico studies of benzothiazole derivatives as potential inhibitors of Anopheles funestus and Anopheles gambiae trehalase"],"prefix":"10.3389","volume":"4","author":[{"given":"Temitope A.","family":"Ogunnupebi","sequence":"first","affiliation":[]},{"given":"Gbolahan O.","family":"Oduselu","sequence":"additional","affiliation":[]},{"given":"Oluwadunni F.","family":"Elebiju","sequence":"additional","affiliation":[]},{"given":"Olayinka O.","family":"Ajani","sequence":"additional","affiliation":[]},{"given":"Ezekiel","family":"Adebiyi","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"105504","DOI":"10.1016\/j.bioorg.2021.105504","article-title":"Synthesis, anticancer evaluation and molecular docking of new benzothiazole scaffolds targeting FGFR-1","volume":"119","author":"Abd El-Meguid","year":"2022","journal-title":"Bioorg. Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"Gromacs: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.3390\/insects13111070","article-title":"Anopheles gambiae trehalase inhibitors for malaria vector control: a molecular docking and molecular dynamics study","volume":"13","author":"Adedeji","year":"2022","journal-title":"Insects"},{"key":"B4","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1186\/s13071-020-04342-5","article-title":"Anopheles metabolic proteins in malaria transmission, prevention and control: a review","volume":"13","author":"Adedeji","year":"2020","journal-title":"Parasit. Vectors"},{"key":"B5","doi-asserted-by":"publisher","first-page":"117793222311582","DOI":"10.1177\/11779322231158254","article-title":"Pharmacophore-aided virtual screening and molecular dynamics simulation identifies TrkB agonists for treatment of CDKL5-deficiency disorders","volume":"17","author":"Ademuwagun","year":"2023","journal-title":"Bioinform. Biol. Insights"},{"key":"B6","doi-asserted-by":"publisher","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":"Akash","year":"2023","journal-title":"Sci. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e0204233","DOI":"10.1371\/journal.pone.0204233","article-title":"Dominant malaria vector species in Nigeria: modelling potential distribution of Anopheles gambiae sensu lato and its siblings with MaxEnt","volume":"13","author":"Akpan","year":"2018","journal-title":"PLoS One"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13321-014-0042-6","article-title":"Quantitative estimation of pesticide-likeness for agrochemical discovery","volume":"6","author":"Avram","year":"2014","journal-title":"J. Cheminform."},{"key":"B10","doi-asserted-by":"publisher","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":"Azzam","year":"2023","journal-title":"Complex Use Min. Resour."},{"key":"B11","unstructured":"Chemyang\n          \n          \n          2019"},{"key":"B12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13321-020-00442-7","article-title":"The ChemicalToolbox: reproducible, user-friendly cheminformatics analysis on the Galaxy platform","volume":"12","author":"Bray","year":"2020","journal-title":"J. Cheminform."},{"key":"B13","doi-asserted-by":"publisher","first-page":"101333","DOI":"10.1371\/journal.pone.0010133","article-title":"Different functions of the insect soluble and membrane-bound trehalase genes in chitin biosynthesis revealed by rna interference","volume":"5","author":"Chen","year":"2010","journal-title":"PLoS One"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e14202","DOI":"10.1371\/journal.pone.0014202","article-title":"De novo transcriptome sequencing in anopheles funestus using illumina RNA-seq technology","volume":"5","author":"Crawford","year":"2010","journal-title":"PLoS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3846","DOI":"10.3390\/molecules27123846","article-title":"Homology modeling and molecular docking approaches for the proposal of novel insecticides against the african malaria mosquito (Anopheles gambiae)","volume":"27","author":"Crisan","year":"2022","journal-title":"Molecules"},{"key":"B16","doi-asserted-by":"publisher","first-page":"giz063","DOI":"10.1093\/gigascience\/giz063","article-title":"A chromosome-scale assembly of the major African malaria vector Anopheles funestus","volume":"8","author":"Ghurye","year":"2019","journal-title":"Gigascience"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/07391102.2020.1776157","article-title":"Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies","author":"Gupta","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3839","DOI":"10.3390\/molecules24213839","article-title":"Heterocycles in medicinal chemistry","volume":"24","author":"Jampilek","year":"2019","journal-title":"Molecules"},{"key":"B19","doi-asserted-by":"publisher","first-page":"D1373","DOI":"10.1093\/nar\/gkac956","article-title":"PubChem 2023 update","volume":"51","author":"Kim","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"270","DOI":"10.22270\/jddt.v12i4-s.5549","article-title":"A review on emerging benzothiazoles: biological aspects","volume":"12","author":"Kumar","year":"2022","journal-title":"J. Drug Deliv. Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"730288","DOI":"10.3389\/fcimb.2021.730288","article-title":"Identification of natural inhibitors against SARS-CoV-2 drugable targets using molecular docking, molecular dynamics simulation, and MM-PBSA approach","volume":"11","author":"Kushwaha","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"130566","DOI":"10.1016\/j.molstruc.2021.130566","article-title":"Design, synthesis, antimicrobial evaluation, and molecular docking of novel chiral urea\/thiourea derivatives bearing indole, benzimidazole, and benzothiazole scaffolds","volume":"1241","author":"Lafzi","year":"2021","journal-title":"J. Mol. Struct."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.12688\/gatesopenres.12957.2","article-title":"A testing cascade to identify repurposed insecticides for next-generation vector control tools: screening a panel of chemistries with novel modes of action against a malaria vector","volume":"3","author":"Lees","year":"2019","journal-title":"Gates Open Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"17504","DOI":"10.1073\/pnas.1316709110","article-title":"Impact of trehalose transporter knockdown on Anopheles gambiae stress adaptation and susceptibility to Plasmodium falciparum infection","volume":"110","author":"Liu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/bs.aihch.2016.04.010","article-title":"Thiazole and isothiazole ring\u2013containing compounds in crop protection","author":"Maienfisch","year":"2017","journal-title":"Advances in heterocyclic chemistry"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1093\/jme\/tjaa004","article-title":"Validamycin A delays development and prevents flight in Aedes aegypti (Diptera: Culicidae)","volume":"57","author":"Marten","year":"2020","journal-title":"J. Med. Entomol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3076","DOI":"10.1016\/j.bmc.2018.02.049","article-title":"Design, synthesis and biological evaluation of benzofuran appended benzothiazepine derivatives as inhibitors of butyrylcholinesterase and antimicrobial agents","volume":"26","author":"Mostofi","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1186\/s12936-020-03295-5","article-title":"Aquatic habitats of the malaria vector Anopheles funestus in rural south - eastern Tanzania","volume":"19","author":"Nambunga","year":"2020","journal-title":"Malar. J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e22112","DOI":"10.1002\/arch.22112","article-title":"Toxicological, biochemical, and in silico investigations of three trehalase inhibitors for new ways to control aphids","volume":"115","author":"Neyman","year":"2024","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"105356","DOI":"10.1016\/j.pestbp.2023.105356","article-title":"Resilience of transfluthrin to oxidative attack by duplicated CYP6P9 variants known to confer pyrethroid resistance in the major malaria mosquito Anopheles funestus","volume":"191","author":"Nolden","year":"2023","journal-title":"Pestic. Biochem. Physiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1022429","DOI":"10.3389\/fmed.2022.1022429","article-title":"Structure-based pharmacophore modeling, virtual screening, and molecular dynamics simulation studies for identification of Plasmodium falciparum 5-aminolevulinate synthase inhibitors","volume":"9","author":"Oduselu","year":"2023","journal-title":"Front. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/1177932219865533","article-title":"Homology modelling and molecular docking studies of selected substituted benzo[d]imidazole-1-yl methyl benzimidamide scaffolds on Plasmodium falciparum adenylosuccinate lyase receptor","volume":"13","author":"Oduselu","year":"2019","journal-title":"Bioinform. Biol. Insights"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e28347","DOI":"10.1371\/journal.pone.0028347","article-title":"Nigeria Anopheles vector database: an overview of 100 years\u2019 research","volume":"6","author":"Okorie","year":"2011","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5772\/intechopen.83554","article-title":"Nipping the malaria vectors in the bud: focus on Nigeria","author":"Olayinka","year":"2019","journal-title":"Malaria"},{"key":"B35","doi-asserted-by":"publisher","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single crystals: a new molecular dynamics method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"key":"B36","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.micpath.2017.11.061","article-title":"The prevalence and drug resistance pattern of extended spectrum \u03b2\u2013lactamases (ESBLs) producing Enterobacteriaceae in Africa","volume":"114","author":"Saravanan","year":"2018","journal-title":"Microb. Pathog."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e7976","DOI":"10.1371\/journal.pone.0007976","article-title":"Comparative analysis of the global transcriptome of Anopheles funestus from Mali, West Africa","volume":"4","author":"Serazin","year":"2009","journal-title":"PLoS One"},{"key":"B38","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1093\/glycob\/cwu125","article-title":"Insect trehalase: physiological significance and potential applications","volume":"25","author":"Shukla","year":"2015","journal-title":"Glycobiology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"133479","DOI":"10.1016\/j.molstruc.2022.133479","article-title":"Thiazole derivatives in medicinal chemistry: recent advancements in synthetic strategies, structure activity relationship and pharmacological outcomes","volume":"1266","author":"Singh","year":"2022","journal-title":"J. Mol. Struct."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21203\/rs.3.rs-3151345\/v1","article-title":"Synthesis, molecular docking, molecular dynamic simulation studies, and anti-tubercular activity evaluation of substituted benzimidazole derivatives","volume":"2024","author":"Thapa","year":"2023","journal-title":"Adv. Pharmacol. Pharm. Sci."},{"key":"B41","unstructured":"Framework for the allocation of limited malaria vaccine supply\n          \n          \n          2022"},{"key":"B42","doi-asserted-by":"publisher","first-page":"W5","DOI":"10.1093\/nar\/gkab255","article-title":"ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties","volume":"49","author":"Xiong","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1021\/acs.jcim.8b00532","article-title":"ADMETopt: a web server for ADMET optimization in drug design via scaffold hopping","volume":"58","author":"Yang","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1178996","DOI":"10.3389\/fphys.2023.1178996","article-title":"Potential inhibitory effects of compounds ZK-PI-5 and ZK-PI-9 on trehalose and chitin metabolism in Spodoptera frugiperda (J. E. Smith)","volume":"14","author":"Zhong","year":"2023","journal-title":"Front. Physiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1002\/jcc.21816","article-title":"SwissParam: a fast force field generation tool for small organic molecules","volume":"32","author":"Zoete","year":"2011","journal-title":"J. Comput. Chem."}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2024.1428539\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T05:13:27Z","timestamp":1723180407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2024.1428539\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,9]]},"references-count":45,"alternative-id":["10.3389\/fbinf.2024.1428539"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2024.1428539","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,9]]},"article-number":"1428539"}}