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Also because of the disruption in malaria prevention services during the COVID\u201019 pandemic, there was an increase in malaria cases in 2021 compared to 2020. Hence, the present study outlined the in silico study, synthesis, and antimalarial evaluation of 1,3,5\u2010triazine hybrids conjugated with PABA\u2010glutamic acid. Docking study revealed higher binding energy compared to the originally bound ligand WR99210, predominant hydrogen bond interaction, and involvement of key amino acid residues, like Arg122, Ser120, and Arg59. Fourteen compounds were synthesized using traditional and microwave synthesis. The in vitro antimalarial evaluation against chloroquine\u2010sensitive 3D7 and resistant Dd2 strain of <jats:italic>Plasmodium falciparum<\/jats:italic> showed a high to moderate activity range. Compounds C1 and B4 showed high efficacy against both strains and a further study revealed that compound C1 is non\u2010cytotoxic against the HEK293 cell line with no acute oral toxicity. In vivo, study was performed for the most potent antimalarial compound C1 to optimize the research work and found to be effectively suppressing parasitemia of <jats:italic>Plasmodium berghei<\/jats:italic> strain in the Swiss albino mice model.<\/jats:p>","DOI":"10.1111\/cbdd.14317","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T01:23:59Z","timestamp":1696296239000},"page":"1336-1352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hybrid <scp>PABA<\/scp>\u2010glutamic acid conjugated 1,3,5\u2010triazine derivatives: Design, synthesis, and antimalarial activity screening targeting <i>Plasmodium falciparum<\/i> dihydro folate reductase enzyme"],"prefix":"10.1111","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1322-4471","authenticated-orcid":false,"given":"Ayesha Aktar Khanam","family":"Choudhury","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Dibrugarh University  Dibrugarh Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathishkumar","family":"Vinayagam","sequence":"additional","affiliation":[{"name":"Periyar University Centre for Postgraduate and Research Studies  Dharmapuri Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayana","family":"Adhikari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Dibrugarh University  Dibrugarh Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashmita","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Dibrugarh University  Dibrugarh Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surajit Kumar","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Dibrugarh University  Dibrugarh Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-4916","authenticated-orcid":false,"given":"Hans Raj","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Dibrugarh University  Dibrugarh Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav Jyoti","family":"Patgiri","sequence":"additional","affiliation":[{"name":"RMRC\u2010ICMR NE Region  Dibrugarh Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/11010081"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13065\u2010017\u20100267\u20103"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010018\u20100911\u20109"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/10629361003770951"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2015.06.016"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.07.039"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20225748"},{"key":"e_1_2_9_9_1","unstructured":"Center for Drug Evaluation and Research. 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