{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:48:33Z","timestamp":1780501713427,"version":"3.54.1"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009157","name":"Jomo Kenyatta University of Agriculture and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009157","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2019,10,17]]},"abstract":"<jats:p>Malaria is the eighth highest contributor to global disease burden with 212 million cases and 429,000 deaths reported in 2015. There is an urgent need to develop multiple target drug to curb growing resistance by <jats:italic>Plasmodia<\/jats:italic> due to use of single target drugs and lack of vaccines. Based on a previous study, 3-chloro-4-(4-chlorophenoxy) aniline (ANI) inhibits <jats:italic>Plasmodia<\/jats:italic> enoyl acyl carrier protein reductase. This study aimed at evaluating the antiplasmodial activity of ANI combinations with artesunate (AS) or chloroquine (CQ) against <jats:italic>P. falciparum in vitro<\/jats:italic> based on the semiautomated microdilution assay and <jats:italic>P. berghei in vivo<\/jats:italic> based on Peters\u2019 4-day test. Data were analysed by linear regression using version 5.5 of Statistica, 2000. From the results, on the one hand, a combination of 1.1\u2009ng\/ml AS and 3.3\u2009<jats:italic>\u03bc<\/jats:italic>g\/ml of ANI inhibited 50% growth of W<jats:sub>2<\/jats:sub>, while a combination of 0.8\u2009ng\/ml of AS and 2.6\u2009<jats:italic>\u03bc<\/jats:italic>g\/ml of ANI inhibited 50% growth of 3D<jats:sub>7<\/jats:sub>. On the other hand, a combination of 22\u2009ng\/ml CQ and 3.7\u2009<jats:italic>\u03bc<\/jats:italic>g\/ml of ANI inhibited 50% growth of W<jats:sub>2<\/jats:sub>, while a combination of 4.6\u2009ng\/ml CQ and 3.1\u2009<jats:italic>\u03bc<\/jats:italic>g\/ml of ANI inhibited 50% growth of 3D<jats:sub>7<\/jats:sub>. In <jats:italic>in vivo<\/jats:italic> assays, a combination of ED<jats:sub>50<\/jats:sub> concentrations of AS and ANI cleared all parasites, while <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mrow><mml:mn>1<\/mml:mn><mml:mo>\/<\/mml:mo><mml:mn>2<\/mml:mn><\/mml:mrow><\/mml:mrow><\/mml:math> and <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mrow><mml:mn>1<\/mml:mn><mml:mo>\/<\/mml:mo><mml:mn>4<\/mml:mn><\/mml:mrow><\/mml:mrow><\/mml:math> ED<jats:sub>50<\/jats:sub> combinations inhibited 67.0% and 35.4% parasite growth, respectively. ED<jats:sub>50<\/jats:sub> combinations of CQ and ANI inhibited 81.0% growth of parasites, while <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:mrow><mml:mn>1<\/mml:mn><mml:mo>\/<\/mml:mo><mml:mn>2<\/mml:mn><\/mml:mrow><\/mml:mrow><\/mml:math> and <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mrow><mml:mrow><mml:mn>1<\/mml:mn><mml:mo>\/<\/mml:mo><mml:mn>4<\/mml:mn><\/mml:mrow><\/mml:mrow><\/mml:math> ED<jats:sub>50<\/jats:sub> combinations inhibited 27.3% and 10.2% parasite growth. Assuming a linear relationship between percentage chemosuppression and combination ratios, only 0.88\u2009mg\/kg of AS combined with 1.68\u2009mg\/kg of ANI or 1.78\u2009mg\/kg of CQ with 3.15\u2009mg\/kg of ANI inhibited 50% parasite growth <jats:italic>in vivo<\/jats:italic>. ANI combinations with AS or CQ are thus potential antimalarial drug combinations if their clinical efficacy and safety are ascertained.<\/jats:p>","DOI":"10.1155\/2019\/5153482","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T19:30:52Z","timestamp":1571340652000},"page":"1-7","source":"Crossref","is-referenced-by-count":2,"title":["Antiplasmodial Activity Assay of 3-Chloro-4-(4-chlorophenoxy) Aniline Combinations with Artesunate or Chloroquine <i>In Vitro<\/i> and in a Mouse Model"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7610-7571","authenticated-orcid":true,"given":"Martin","family":"Wekesa Sifuna","sequence":"first","affiliation":[{"name":"Biochemistry Department, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-8713","authenticated-orcid":true,"given":"Milka","family":"Wambui","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kang\u2019ethe Nganga","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Wainaina Kariuki","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Thuo","family":"Kimani","sequence":"additional","affiliation":[{"name":"Centre for Biotechnology Research and Development, Kenya Medical Research Institute (KEMRI), P.O. Box 54840, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Wamakima","family":"Muregi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Mount Kenya University, P.O. Box 342, Thika, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","year":"2014"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2011.03.012"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2010.05.013"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2012.026"},{"issue":"5","key":"5","first-page":"1","volume":"16","year":"2014","journal-title":"Emergency Medicine Practice"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-010-2232-0"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-144"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-012-2886-x"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104063108"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.07.011"},{"issue":"6","key":"11","year":"2012","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2015.03.004"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1128\/ec.00264-13"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1128\/aac.16.6.710"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1984.33.772"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1006\/expr.1995.1049"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/137.2.122"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1975.11686997"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.2149\/tmh.32.15"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1016\/0001-706x(93)90083-n"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0550-5"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.13.18"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0561-2"},{"issue":"1","key":"25","first-page":"72","volume":"4","year":"2005","journal-title":"African Journal of Biotechnology"}],"container-title":["BioMed Research International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2019\/5153482.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2019\/5153482.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2019\/5153482.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T19:30:55Z","timestamp":1571340655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/bmri\/2019\/5153482\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,17]]},"references-count":25,"alternative-id":["5153482","5153482"],"URL":"https:\/\/doi.org\/10.1155\/2019\/5153482","relation":{},"ISSN":["2314-6133","2314-6141"],"issn-type":[{"value":"2314-6133","type":"print"},{"value":"2314-6141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,17]]}}}