{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:07:13Z","timestamp":1789895233710,"version":"4.0.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasitol Res"],"published-print":{"date-parts":[[2023,4]]},"DOI":"10.1007\/s00436-023-07801-x","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T04:36:12Z","timestamp":1677731772000},"page":"979-988","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models"],"prefix":"10.1007","volume":"122","author":[{"given":"Milka Wambui","family":"Waithera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Wekesa","family":"Sifuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Wainaina","family":"Kariuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnson Kang\u2019ethe","family":"Kinyua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Thuo","family":"Kimani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph Kang\u2019ethe","family":"Ng\u2019ang\u2019a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Takei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"7801_CR1","doi-asserted-by":"publisher","first-page":"102526","DOI":"10.1016\/j.parint.2021.102526","volume":"87","author":"F Angrisano","year":"2022","unstructured":"Angrisano F, Robinson LJ (2022) Plasmodium vivax-how hidden reservoirs hinder global malaria elimination. Par Int 87:102526. https:\/\/doi.org\/10.1016\/j.parint.2021.102526","journal-title":"Par Int"},{"issue":"1","key":"7801_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1475-2875-13-339","volume":"13","author":"RM Beteck","year":"2014","unstructured":"Beteck RM, Smit FJ, Haynes RK, N\u2019Da DD (2014) Recent progress in the development of anti-malarial quinolones. Mal J 13(1):1\u201310","journal-title":"Mal J"},{"issue":"45","key":"7801_CR3","doi-asserted-by":"publisher","first-page":"17579","DOI":"10.1073\/pnas.0804338105","volume":"105","author":"F Cosl\u00e9dan","year":"2008","unstructured":"Cosl\u00e9dan F, Fraisse L, Pellet A, Guillouc F, Mordmullerd B, Kremsnerd GP, Morenf A, Mazierf D, Maffrand J, Meunier B (2008) Selection of a trioxaquine as an antimalarial drug candidate. PNAS 105(45):17579\u201317584","journal-title":"PNAS"},{"key":"7801_CR4","doi-asserted-by":"publisher","first-page":"102623","DOI":"10.1016\/j.parint.2022.102623","volume":"91","author":"P Cravo","year":"2022","unstructured":"Cravo P (2022) On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria. Par Int 91:102623. https:\/\/doi.org\/10.1016\/j.parint.2022.102623","journal-title":"Par Int"},{"issue":"1","key":"7801_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-015-1032-5","volume":"14","author":"NS Dambuza","year":"2015","unstructured":"Dambuza NS, Smith P, Evans A, Norman J, Taylor D, Andayi A, Egan T, Chibale K, Wiesner L (2015) Antiplasmodial activity, in vivo pharmacokinetics and anti-malarial efficacy evaluation of hydroxypyridinone hybrids in a mouse model. Mal J 14(1):1\u20138","journal-title":"Mal J"},{"issue":"12","key":"7801_CR6","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.2174\/138955709789957323","volume":"9","author":"M Dhanawat","year":"2009","unstructured":"Dhanawat M, Das N, Nagarwal RC, Shrivastava SK (2009) Antimalarial drug development: past to present scenario. Mini-Rev Med Chem 9(12):1447\u20131469","journal-title":"Mini-Rev Med Chem"},{"issue":"4","key":"7801_CR7","first-page":"1","volume":"53","author":"C Dohutia","year":"2017","unstructured":"Dohutia C, Chetia D, Gogoi K, Bhattacharyya DR, Sarma K (2017) Molecular docking, synthesis and in vitro antimalarial evaluation of certain novel curcumin analogues. Braz J Pharm Sci 53(4):1\u201314","journal-title":"Braz J Pharm Sci"},{"issue":"3","key":"7801_CR8","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1002\/med.21643","volume":"40","author":"LS Feng","year":"2020","unstructured":"Feng LS, Xu Z, Chang L, Li C, Yan X, Gao C, Ding C, Zhao F, Shi F, Wu X (2020) hybrid molecules with potential in vitro antiplasmodial and in vivo antimalarial activity against drug-resistant Plasmodium falciparum. Med Res Rev 40(3):931\u2013971","journal-title":"Med Res Rev"},{"issue":"7","key":"7801_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21072536","volume":"21","author":"I Gessner","year":"2020","unstructured":"Gessner I, Neundorf I (2020) Nanoparticles modified with cell-penetrating peptides: conjugation mechanisms, physicochemical properties, and application in cancer diagnosis and therapy. Int J Mol Sci 21(7):1\u201321","journal-title":"Int J Mol Sci"},{"issue":"1","key":"7801_CR10","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.apjtb.2016.11.001","volume":"7","author":"B Hermansyah","year":"2017","unstructured":"Hermansyah B, Fitri LE, Sardjono TW, Endharti AT, Arifin S, Budiarti N, Candradikusuma D, Sulistyaningsih E, Berens-Riha N (2017) Clinical features of severe malaria: protective effect of mixed plasmodial malaria. Asian Pac J Trop Biomed 7(1):4\u20139","journal-title":"Asian Pac J Trop Biomed"},{"issue":"12","key":"7801_CR11","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1016\/j.apjtb.2017.09.017","volume":"7","author":"N Horata","year":"2017","unstructured":"Horata N, Choowongkomon K, Ratanabunyong S, Tongshoob J, Khusmith S (2017) Acquisition of naturally acquired antibody response to Plasmodium falciparum erythrocyte membrane protein 1-dbl\u03b1 and differential regulation of igg subclasses in severe and uncomplicated malaria. Asian Pac J Trop Biomed 7(12):1055\u20131061. https:\/\/doi.org\/10.1016\/j.apjtb.2017.09.017","journal-title":"Asian Pac J Trop Biomed"},{"key":"7801_CR12","doi-asserted-by":"crossref","unstructured":"Jonsson M, Jestoi M, Nathanail AV, Kokkonen UM, Anttila M, Koivisto P, Karhunen P, Peltonen K (2013) Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin. Food Chem Toxicol 53(2013):27\u201332","DOI":"10.1016\/j.fct.2012.11.023"},{"issue":"6","key":"7801_CR13","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1007\/s00436-019-06335-5","volume":"118","author":"H Joseph","year":"2019","unstructured":"Joseph H, Eriksson E, Schofield L (2019) Early suppression of B cell immune responses by low doses of chloroquine and pyrimethamine: implications for studying immunity in malaria. Par Res 118(6):1987\u20131992","journal-title":"Par Res"},{"issue":"5","key":"7801_CR14","first-page":"34","volume":"7","author":"FM Khan","year":"2017","unstructured":"Khan FM, Bari MA, Islam MK, Islam MD, Kayser MS, Nahar N, Faruk MA, Rashid MA (2017) The natural anti-tubercular agents: in silico study of physicochemical, pharmacokinetic and toxicological properties. J App Pharm Sci 7(5):34\u201338","journal-title":"J App Pharm Sci"},{"issue":"2","key":"7801_CR15","first-page":"G233","volume":"317","author":"T Kn\u00f6pfel","year":"2019","unstructured":"Kn\u00f6pfel T, Himmerkus N, G\u00fcnzel D, Bleich M, Hernando N, Wagner CA (2019) Paracellular transport of phosphate along the intestine. Am J Physi-Gastro Liver Physi 317(2):G233\u2013G241","journal-title":"Am J Physi-Gastro Liver Physi"},{"issue":"1","key":"7801_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1475-2875-12-71","volume":"12","author":"M Lombard","year":"2013","unstructured":"Lombard M, N\u2019Da DD, Van Ba CT, Wein S, Norman J, Weisner L, Vial H (2013) Potent in vivo anti-malarial activity and representative snapshot pharmacokinetic evaluation of artemisinin-quinoline hybrids. Mal J 12(1):1\u20137","journal-title":"Mal J"},{"issue":"3","key":"7801_CR17","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1021\/ml3000808","volume":"3","author":"S Manohar","year":"2012","unstructured":"Manohar S, Rajesh CU, Khan SI, Tekwani BL, Rawat DS (2012) Novel 4-aminoquinoline-pyrimidine based hybrids with improved in vitro and in vivo antimalarial activity. ACS Med Chem Let 3(3):555\u2013559","journal-title":"ACS Med Chem Let"},{"key":"7801_CR18","doi-asserted-by":"crossref","unstructured":"Mehmood Y, Khan IU, Shahzad Y, Khan RU, Igbal MS, Khan HA, Yousaf AM, Khalid SH, Asghar S, Asif M, Hussain T, Shah SU (2020) In vitro and in vivo evaluation of velpatasvir-loaded mesoporous silica scaffolds. A prospective carrier for drug bioavailability enhancement. Pharmaceutics 12(307):1\u201318","DOI":"10.3390\/pharmaceutics12040307"},{"issue":"1","key":"7801_CR19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1021\/ar7000843","volume":"41","author":"B Meunier","year":"2008","unstructured":"Meunier B (2008) Hybrid molecules with a dual mode of action: dream or reality. Acco Chemi Res 41(1):69\u201377","journal-title":"Acco Chemi Res"},{"issue":"80","key":"7801_CR20","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immu Meth 65(80):55\u201363","journal-title":"J Immu Meth"},{"issue":"10","key":"7801_CR21","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/nrd3801","volume":"11","author":"PY Muller","year":"2012","unstructured":"Muller PY, Milton MN (2012) The determination and interpretation of the therapeutic index in drug development. Nat Re Drug Disc 11(10):751\u2013761","journal-title":"Nat Re Drug Disc"},{"issue":"1","key":"7801_CR22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/ddr.20345","volume":"71","author":"FW Muregi","year":"2010","unstructured":"Muregi FW, Ishih A (2010) Next-generation antimalarial drugs: hybrid molecules as a new strategy in drug design. Drug Dev Res 71(1):20\u201332","journal-title":"Drug Dev Res"},{"key":"7801_CR23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2020.00001","volume":"11","author":"NN Nghochuzie","year":"2020","unstructured":"Nghochuzie NN, Olwal CO, Uduokang AJ, Amang-Etego LN, Amambua-Ngwa A (2020) Pausing the fight against malaria to combat the COVID-19 pandemic in Africa: is the future of malaria bleak? Fron Microbiol 11:1\u20135","journal-title":"Fron Microbiol"},{"issue":"9","key":"7801_CR24","doi-asserted-by":"publisher","first-page":"3818","DOI":"10.1021\/jm500147k","volume":"57","author":"A Nilsen","year":"2014","unstructured":"Nilsen A, Miley GP, Forquer IP, Mather MW, Katneni K, Li Y, Pou S, Pershing AM, Stickles AM, Ryan E, Kelly JX, Doggett JS, White KL, Hinrichs DJ, Winter RW, Charman SA, Zakharov LN, Bathurst I, Burrows JN, Vaidya AB, Riscoe MK (2014) Discovery, synthesis, and optimization of antimalarial 4(1 H)-quinolone-3-diarylethers. J Med Chem 57(9):3818\u20133834","journal-title":"J Med Chem"},{"issue":"1","key":"7801_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-017-1917-6","volume":"16","author":"OC Odhiambo","year":"2017","unstructured":"Odhiambo OC, Wamakima HN, Magoma GN, Kirira PG, Malala BJ, Kimani FT, Muregi FW (2017) Efficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model. Mal J 16(1):1\u20139","journal-title":"Mal J"},{"issue":"1","key":"7801_CR26","first-page":"3865","volume":"9","author":"WN Omwoyo","year":"2014","unstructured":"Omwoyo WN, Ogutu B, Oloo F, Swai H, Kalombo L, Melariri P, Mahanga GM, Gathirwa JW (2014) Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles. Int J Nanomed 9(1):3865\u20133874","journal-title":"Int J Nanomed"},{"issue":"3","key":"7801_CR27","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1007\/s13346-020-00823-3","volume":"11","author":"R Parhi","year":"2021","unstructured":"Parhi R, Mandru A (2021) Enhancement of skin permeability with thermal ablation techniques: concept to commercial products. Drug Deliv Trans Res 11(3):817\u2013841","journal-title":"Drug Deliv Trans Res"},{"issue":"2","key":"7801_CR28","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1080\/00034983.1975.11686997","volume":"69","author":"W Peters","year":"1975","unstructured":"Peters W, Portus JH, Robinson BL (1975) The chemotherapy of rodent malaria, XXII. Ann Trop Med Paras 69(2):155\u2013171. https:\/\/doi.org\/10.1080\/00034983.1975.11686997","journal-title":"Ann Trop Med Paras"},{"issue":"2","key":"7801_CR29","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/cbdd.12289","volume":"84","author":"M Sharma","year":"2014","unstructured":"Sharma M, Chauhan K, Srivastava RK, Singh SV, Srivastava K, Saxena JK, Puri SK, Chauhan MS (2014) Design and synthesis of a new class of 4-aminoquinolinyl- and 9-anilinoacridinyl schiff base hydrazones as potent antimalarial agents. Chem Biol Drug Des 84(2):175\u2013181","journal-title":"Chem Biol Drug Des"},{"key":"7801_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/5153482","volume":"2019","author":"MW Sifuna","year":"2019","unstructured":"Sifuna MW, Wambui M, Nganga JK, Kariuki DW, Kimani FT, Muregi FW (2019) Antiplasmodial activity assay of 3-Chloro-4- (4-Chlorophenoxy ) aniline combinations with artesunate or chloroquine in vitro and in a mouse model. BioMed Res Int 2019:1\u20137","journal-title":"BioMed Res Int"},{"issue":"04","key":"7801_CR31","doi-asserted-by":"publisher","first-page":"47","DOI":"10.4236\/cmb.2014.44006","volume":"04","author":"NSR Silva","year":"2014","unstructured":"Silva NSR, Gon\u00e7alves LKS, Duarte JL, Silva JS, Santos CF, Braga FS, Silva RC, Costa JS, Hage-Melim LIS, Dos Santos CBR (2014) Computational analysis of physicochemical, pharmacokinetic and toxicological properties of deoxyhypusine synthase inhibitors with antimalarial activity. Comp Mol Biosci 04(04):47\u201357","journal-title":"Comp Mol Biosci"},{"issue":"2021","key":"7801_CR32","doi-asserted-by":"publisher","first-page":"102525","DOI":"10.1016\/j.parint.2021.102525","volume":"87","author":"M Tachibana","year":"2022","unstructured":"Tachibana M, Takashima E, Morita M, Sattabongkot J, Ishino T, Culleton R, Torii M, Tsuboi T (2022) Plasmodium vivax transmission-blocking vaccines: progress, challenges and innovation. Par Int 87(2021):102525. https:\/\/doi.org\/10.1016\/j.parint.2021.102525","journal-title":"Par Int"},{"key":"7801_CR33","doi-asserted-by":"crossref","unstructured":"Trager W, Jensen BJ (1976) Human malaria parasites in continous culture. Reports 193(4254):673\u201375","DOI":"10.1126\/science.781840"},{"issue":"4","key":"7801_CR34","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1124\/mol.118.114751","volume":"95","author":"JN Tschirhart","year":"2019","unstructured":"Tschirhart JN, Li W, Guo J, Zhang S (2019) Blockade of the human ether a-go-go\u2013related gene (hERG) potassium channel. Mol Pharm 95(4):386\u2013397","journal-title":"Mol Pharm"},{"issue":"11","key":"7801_CR35","doi-asserted-by":"publisher","first-page":"3868","DOI":"10.1128\/AAC.00510-08","volume":"52","author":"FDP Varotti","year":"2008","unstructured":"Varotti FDP, Botelho ACC, Andrade AA, Paula RC, Fagundes EMS, Valverde A, Mayer LMU, Mendonca JS, Souza MVN, Boechat N, Krettli AU (2008) Synthesis, antimalarial activity, and intracellular targets of mefas, a new hybrid compound derived from mefloquine and artesunate. Antimic Agents Chem 52(11):3868\u20133874","journal-title":"Antimic Agents Chem"},{"issue":"2","key":"7801_CR36","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1002\/jps.10118","volume":"91","author":"YH Zhao","year":"2002","unstructured":"Zhao YH, Le J, Abraham MH, Hersey A, Eddershaw PJ, Luscombe CN, Boutina D, Beck G, Brad S, Cooper I, Platts JA (2002) Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors. J Pharm Sci 91(2):605","journal-title":"J Pharm Sci"}],"container-title":["Parasitology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00436-023-07801-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00436-023-07801-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00436-023-07801-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T14:56:56Z","timestamp":1744210616000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00436-023-07801-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["7801"],"URL":"https:\/\/doi.org\/10.1007\/s00436-023-07801-x","relation":{},"ISSN":["0932-0113","1432-1955"],"issn-type":[{"value":"0932-0113","type":"print"},{"value":"1432-1955","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,2]]},"assertion":[{"value":"7 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by KEMRI\u2019s ACUC, KEMRI-ACU 01\/10\/2018.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}