{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:02:08Z","timestamp":1778691728274,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A series of nine substituted derivatives of 4\u2010methyl\u20102\u2010(3\u2010methyl\u20102\u2010(4\u2010methylphenylsulfonamido)\u2010butanamido)thiazole\u20105\u2010carboxylate were synthesized, characterized, and evaluated for antimalarial activity. The synthesis involved a two\u2010step process using methyl acetoacetate and various substituted benzenesulfonamoyl alkanamides. Structural confirmation was achieved using NMR and mass spectroscopy. The in vivo antimalarial efficacy was tested against <jats:italic>Plasmodium berghei<\/jats:italic> in Swiss albino mice, with artemisinin as the reference drug. Compounds <jats:bold>4e<\/jats:bold> and <jats:bold>4h<\/jats:bold> exhibited the highest inhibition rates of 81.68% and 85.34%, respectively, closely matching artemisinin (90%). Structure\u2013activity relationship (SAR) analysis identified the sulfonamide group, alkyl chain length, and molecular flexibility as critical determinants of activity. Docking studies revealed strong binding affinities for <jats:bold>4e<\/jats:bold> and <jats:bold>4h<\/jats:bold>, supported by stable hydrogen bonds and hydrophobic interactions with the enzyme's active site, corroborated by molecular dynamics simulations. ADMET analysis revealed favorable pharmacokinetic and safety profiles, including high GI absorption, acceptable solubility, and low mutagenic risk. These findings highlight compounds <jats:bold>4e<\/jats:bold> and <jats:bold>4h<\/jats:bold> as promising leads for antimalarial drug development.<\/jats:p>","DOI":"10.1002\/cbdv.202403504","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:48:13Z","timestamp":1742950093000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design, Synthesis, In Vivo Antimalarial Activity, and In Silico Studies of Sulfonamide\u2010Alkanamido Thiazole\u20105\u2010Carboxylate Derivatives"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-6954","authenticated-orcid":false,"given":"James A.","family":"Ezugwu","sequence":"first","affiliation":[{"name":"Department of Pure and Industrial Chemistry University of Nigeria  Nsukka Nigeria"},{"name":"Organic Synthesis and Processing Chemistry Division CSIR\u2010India Institute of Chemical Technology  Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David I.","family":"Ugwu","sequence":"additional","affiliation":[{"name":"Department of Pure and Industrial Chemistry University of Nigeria  Nsukka Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8172-6633","authenticated-orcid":false,"given":"Mithun","family":"Rudrapal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Biotechnology and Pharmaceutical Sciences Vignan's Foundation for Science, Technology and Research  Guntur India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gourav","family":"Rakshit","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology Birla Institute of Technology (BIT)  Ranchi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology Birla Institute of Technology (BIT)  Ranchi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurma S.","family":"Hariprasad","sequence":"additional","affiliation":[{"name":"Organic Synthesis and Processing Chemistry Division CSIR\u2010India Institute of Chemical Technology  Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel O.","family":"Abonyi","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Enugu State University College of Medicine  Enugu Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(24)00016-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanmic.2024.101035"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2024.107508"},{"key":"e_1_2_10_5_1","volume-title":"WHO Guidelines for Malaria","author":"World Health Organization","year":"2023"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21144986"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-144"},{"key":"e_1_2_10_8_1","first-page":"93","volume-title":"Studies in Natural Products Chemistry","author":"Ningthoujam S. 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