{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:07:00Z","timestamp":1780466820268,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":152,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005864","name":"National Commission for Science, Technology and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biochemistry Research International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Despite the urgent need for new therapies to treat multidrug\u2010resistant virulent\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    , many promising antimalarial candidates fail to progress to clinical use because their pharmacokinetic (PK) profile is poorly characterized. This study predicted the PK profile of a new compound, 3\u2010chloro\u20104\u2010(4\u2010chlorophenoxy)aniline (ANI), in silico using the pkCSM online platform. In vitro cytotoxicity in Vero E6 cells and antiplasmodial activity against chloroquine\u2010sensitive (\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    3D7) and chloroquine\u2010resistant (\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    W2) strains were screened using the MTT colorimetric and the [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010hypoxanthine incorporation assays, respectively. In vivo antimalarial efficacy was evaluated in\n                    <jats:italic>Plasmodium berghei<\/jats:italic>\n                    ANKA and piperaquine\u2010resistant (PQ\n                    <jats:sup>R<\/jats:sup>\n                    )\n                    <jats:italic>P. berghei<\/jats:italic>\n                    parasites in mouse models employing early and established infection tests.\n                    <jats:italic>In silico<\/jats:italic>\n                    predictions show that ANI is a substrate for CYP 3A4 and CYP 2D6 and is unlikely to inhibit the hERG potassium ion channel. ANI exhibited low cytotoxicity, with a CC\n                    <jats:sub>50<\/jats:sub>\n                    value of 7.90\u2009\u00d7\u200910\n                    <jats:sup>2<\/jats:sup>\n                    \u2009\u00b1\u200986.40\u2009\u03bcM, and potent antiplasmodial activity, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 1.72\u2009\u00b1\u20090.09\u2009\u03bcM and 1.84\u2009\u00b1\u20090.21\u2009\u03bcM against the 3D7 and W2 strains, respectively. The selectivity index of greater than 400 indicates that ANI has a broad safety margin. In vivo, ANI demonstrated antimalarial efficacy with ED\n                    <jats:sub>50<\/jats:sub>\n                    values of 3.07\u2009mg\/kg\/day against\n                    <jats:italic>P. berghei<\/jats:italic>\n                    ANKA and 2.81\u2009mg\/kg\/day against PQ\n                    <jats:sup>R<\/jats:sup>\n                    <jats:italic>P. berghei<\/jats:italic>\n                    parasites. Notably, mice treated with ANI in the established infection model survived for up to 30\u2009days without observable adverse effects. These findings highlight ANI as a potential antimalarial compound and support further drug evaluation and development.\n                  <\/jats:p>","DOI":"10.1155\/bri\/6509347","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:32:32Z","timestamp":1780464752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>In Silico<\/i>\n                    Pharmacokinetic Profile and Antimalarial Efficacy of 3\u2010Chloro\u20104\u2010(4\u2010Chlorophenoxy)Aniline"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-8713","authenticated-orcid":false,"given":"Milka W.","family":"Waithera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadrack K.","family":"Kimani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Njoroge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Nyahanga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnson K.","family":"Kinyua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_11_1_2","volume-title":"World Malaria Report 2023","author":"WHO","year":"2023"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-023-07801-x"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2023.107012"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2021.04.003"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2020.11.024"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.13172\/2054-4057-1-1-1119"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.4236\/cmb.2014.44006"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.9734\/ijbcrr\/2017\/29473"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-020-03174-z"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12918-016-0291-2"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5153482"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.22159\/ajpcr.2017.v10i9.19337"},{"key":"e_1_2_11_13_2","first-page":"899","article-title":"Prediction of In-Silico ADME Properties of 1,2-O-Isopropylidene Aldohexose Derivatives","volume":"13","author":"Kova\u010devi\u0107 S. 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