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Herein, we designed and synthesized some structurally novel benzotriazole\u2010<jats:italic>\u03b2<\/jats:italic>\u2010lactams using 2\u2010(1<jats:italic>H<\/jats:italic>\u2010benzo[<jats:italic>d<\/jats:italic>][1,2,3]triazol\u20101\u2010yl)acetic acid as a key intermediate. To synthesize the target molecules, the ketene\u2010imine cycloaddition reaction was employed. First, The reaction of 1<jats:italic>H<\/jats:italic>\u2010benzo[<jats:italic>d<\/jats:italic>][1,2,3]triazole with 2\u2010bromoacetic acid in aqueous sodium hydroxide yielded 2\u2010(1<jats:italic>H<\/jats:italic>\u2010benzo[<jats:italic>d<\/jats:italic>][1,2,3]triazol\u20101\u2010yl)acetic acid. Then, the treatment of 2\u2010(1<jats:italic>H<\/jats:italic>\u2010benzo[<jats:italic>d<\/jats:italic>][1,2,3]triazol\u20101\u2010yl)acetic acid with tosyl chloride, triethyl amine, and Schiff base provided new <jats:italic>\u03b2<\/jats:italic>\u2010lactams in good to moderate yields.The formation of all cycloadducts was confirmed by elemental analysis, FT\u2010IR, NMR and mass spectral data. Moreover, X\u2010ray crystallography was used to determine the relative stereochemistry of <jats:bold>4a<\/jats:bold> compound. The <jats:italic>in\u2005vitro<\/jats:italic> antimalarial activity test was conducted for each compound against <jats:italic>P. falciparum<\/jats:italic> K1. The IC<jats:sub>50<\/jats:sub> values ranged from 5.56 to 25.65\u2005\u03bcM. A cytotoxicity profile of the compounds at 200\u2005\u03bcM final concentration revealed suitable selectivity of the compounds for malaria treatment. Furthermore, the docking study was carried out for each compound into the <jats:italic>P. falciparum<\/jats:italic> dihydrofolate reductase enzyme (PfDHFR) binding site to analyze their possible binding orientation in the active site.<\/jats:p>","DOI":"10.1002\/cbdv.202301745","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T07:18:25Z","timestamp":1704784705000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel Benzotriazole\u2010<i>\u03b2<\/i>\u2010lactam Derivatives as Antimalarial Agents: Design, Synthesis, Biological Evaluation and Molecular Docking Studies"],"prefix":"10.1002","volume":"21","author":[{"given":"Malihe","family":"Aye","sequence":"first","affiliation":[{"name":"Department of Chemistry College of Sciences Shiraz University  Shiraz 71946-84795 Iran"},{"name":"Department of Civil and Environmental Engineering Shiraz University  Shiraz 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