{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:26:25Z","timestamp":1791905185250,"version":"4.3.4"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"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":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2024,6]]},"DOI":"10.1007\/s00210-023-02815-9","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T05:02:05Z","timestamp":1700802125000},"page":"4013-4024","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In vitro and in vivo antiplasmodial activity of a synthetic dihydroartemisinin\u2013eosin B hybrid"],"prefix":"10.1007","volume":"397","author":[{"given":"Hajar Karimi","family":"Askarani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azar","family":"Tahghighi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdieh","family":"Ahmadpoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Zamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"issue":"5","key":"2815_CR1","doi-asserted-by":"publisher","first-page":"e00249","DOI":"10.1128\/AAC.00249-17","volume":"61","author":"D Agarwal","year":"2017","unstructured":"Agarwal D, Gupta RD, Awasthi SK (2017) Are antimalarial hybrid molecules a close reality or a distant dream? Antimicrob Agents Chemother 61(5):e00249-e317","journal-title":"Antimicrob Agents Chemother"},{"issue":"10","key":"2815_CR2","doi-asserted-by":"publisher","first-page":"061","DOI":"10.7324\/JAPS.2019.91008","volume":"9","author":"U Ajima","year":"2019","unstructured":"Ajima U, Onah JO, Wannang NN (2019a) Synthesis and antiplasmodial evaluation of a ciprofloxacin-dihydroartemisinin conjugate. J Appl Pharm Sci 9(10):061\u2013067","journal-title":"J Appl Pharm Sci"},{"issue":"1","key":"2815_CR3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.13171\/mjc91190822625ua","volume":"9","author":"U Ajima","year":"2019","unstructured":"Ajima U, Onah JO, Wannang NN (2019b) Synthesis, characterization and biological evaluation of benzimidazole-dihydroartemisinin hybrids as potential dual acting antimalarial agents. Mediterr J Chem 9(1):52\u201364","journal-title":"Mediterr J Chem"},{"issue":"1","key":"2815_CR4","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.molbiopara.2009.09.005","volume":"169","author":"RJ Allen","year":"2010","unstructured":"Allen RJ, Kirk K (2010) Plasmodium falciparum culture: the benefits of shaking. Mol Biochem Parasitol 169(1):63\u201365","journal-title":"Mol Biochem Parasitol"},{"key":"2815_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113454","volume":"220","author":"EK Aratikatla","year":"2021","unstructured":"Aratikatla EK, Kalamuddin M, Rana KC, Datta G, Asad M, Sundararaman S et al (2021) Combating multi-drug resistant malaria parasite by inhibiting falcipain-2 and heme-polymerization: artemisinin-peptidyl vinyl phosphonate hybrid molecules as new antimalarials. Eur J Med Chem 220:113454","journal-title":"Eur J Med Chem"},{"issue":"1","key":"2815_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-022-04079-9","volume":"21","author":"Q Bassat","year":"2022","unstructured":"Bassat Q, Ma\u00efga-Ascofar\u00e9 O, May J, Clain J, Mombo-Ngoma G, Groger M et al (2022) Challenges in the clinical development pathway for triple and multiple drug combinations in the treatment of uncomplicated falciparum malaria. Malar J 21(1):1\u20138","journal-title":"Malar J"},{"issue":"19","key":"2815_CR7","doi-asserted-by":"publisher","first-page":"7895","DOI":"10.1021\/acs.jmedchem.5b01036","volume":"58","author":"M Bertinaria","year":"2015","unstructured":"Bertinaria M, Orjuela-Sanchez P, Marini E, Guglielmo S, Hofer A, Martins YC et al (2015) NO-donor dihydroartemisinin derivatives as multitarget agents for the treatment of cerebral malaria. J Med Chem 58(19):7895\u20137899","journal-title":"J Med Chem"},{"issue":"1","key":"2815_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1475-2875-11-132","volume":"11","author":"P Byakika-Kibwika","year":"2012","unstructured":"Byakika-Kibwika P, Lamorde M, Mayito J, Nabukeera L, Mayanja-Kizza H, Katabira E et al (2012) Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults. Malar J 11(1):1\u20136","journal-title":"Malar J"},{"issue":"10","key":"2815_CR9","doi-asserted-by":"publisher","first-page":"4698","DOI":"10.1128\/AAC.05133-11","volume":"55","author":"R Capela","year":"2011","unstructured":"Capela R, Cabal GG, Rosenthal PJ, Gut J, Mota MM, Moreira R et al (2011) Design and evaluation of primaquine-artemisinin hybrids as a multistage antimalarial strategy. Antimicrob Agents Chemother 55(10):4698\u20134706","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"2815_CR10","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"T-C Chou","year":"2010","unstructured":"Chou T-C (2010) Drug combination studies and their synergy quantification using the Chou-Talalay MethodSynergy quantification method. Can Res 70(2):440\u2013446","journal-title":"Can Res"},{"issue":"5","key":"2815_CR11","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.jpha.2020.07.005","volume":"11","author":"N Erhunse","year":"2021","unstructured":"Erhunse N, Sahal D (2021) Protecting future antimalarials from the trap of resistance: lessons from artemisinin-based combination therapy (ACT) failures. J Pharm Anal 11(5):541\u2013554","journal-title":"J Pharm Anal"},{"issue":"6","key":"2815_CR12","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1021\/acsomega.7b00310","volume":"2","author":"T Fr\u00f6hlich","year":"2017","unstructured":"Fr\u00f6hlich T, Reiter C, Ibrahim MM, Beutel J, Hutterer C, Zeittr\u00e4ger I et al (2017) Synthesis of novel hybrids of quinazoline and artemisinin with high activities against Plasmodium falciparum, human cytomegalovirus, and leukemia cells. ACS Omega 2(6):2422\u20132431","journal-title":"ACS Omega"},{"key":"2815_CR13","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1007\/s00210-021-02085-3","volume":"394","author":"G Kayki-Mutlu","year":"2021","unstructured":"Kayki-Mutlu G, Michel MC (2021) A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020. Naunyn-Schmiedeberg\u2019s Arch Pharmacol 394:839\u2013852","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"},{"issue":"1","key":"2815_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-022-04140-7","volume":"21","author":"VS Koko","year":"2022","unstructured":"Koko VS, Warsame M, Vonhm B, Jeuronlon MK, Menard D, Ma L et al (2022) Artesunate\u2013amodiaquine and artemether\u2013lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia: in vivo efficacy and frequency of molecular markers. Malar J 21(1):1\u201315","journal-title":"Malar J"},{"issue":"10335","key":"2815_CR15","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1016\/S0140-6736(22)00729-2","volume":"399","author":"T Lancet","year":"2022","unstructured":"Lancet T (2022) Malaria in 2022: a year of opportunity. Lancet (london, England) 399(10335):1573","journal-title":"Lancet (london, England)"},{"issue":"1","key":"2815_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-018-2281-x","volume":"17","author":"L Lobo","year":"2018","unstructured":"Lobo L, Cabral LI, Sena MI, Guerreiro B, Rodrigues AS, de Andrade-Neto VF et al (2018) New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum. Malar J 17(1):1\u201311","journal-title":"Malar J"},{"key":"2815_CR17","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/1475-2875-12-71","volume":"12","author":"M Lombard","year":"2013","unstructured":"Lombard M, N\u2019Da DDTVB (2013) C, Wein S, Norman J, Wiesner L, Vial H: Potent in vivo anti-malarial activity and representative snapshot pharmacokinetic evaluation of artemisinin-quinoline hybrids. Malar J 12:71","journal-title":"Malar J"},{"issue":"6","key":"2815_CR18","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1016\/j.bmcl.2011.01.103","volume":"21","author":"MC Lombard","year":"2011","unstructured":"Lombard MC, N\u2019Da DD, Breytenbach JC, Smith PJ, Lategan CA (2011) Synthesis, in vitro antimalarial and cytotoxicity of artemisinin-aminoquinoline hybrids. Bioorg Med Chem Lett 21(6):1683\u20131686","journal-title":"Bioorg Med Chem Lett"},{"issue":"7","key":"2815_CR19","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1039\/D0NP00079E","volume":"38","author":"H-N Lyu","year":"2021","unstructured":"Lyu H-N, Ma N, Meng Y, Zhang X, Wong Y-K, Xu C et al (2021) Study towards improving artemisinin-based combination therapies. Nat Prod Rep 38(7):1243\u20131250","journal-title":"Nat Prod Rep"},{"issue":"9","key":"2815_CR20","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1128\/AAC.00621-06","volume":"50","author":"KM Massimine","year":"2006","unstructured":"Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, Sirawaraporn W et al (2006) Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. Antimicrob Agents Chemother 50(9):3132\u20133141","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"2815_CR21","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? Acc Chem Res 41(1):69\u201377","journal-title":"Acc Chem Res"},{"key":"2815_CR22","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.ejmech.2016.08.039","volume":"124","author":"S Mishra","year":"2016","unstructured":"Mishra S, Singh P (2016) Hybrid molecules: the privileged scaffolds for various pharmaceuticals. Eur J Med Chem 124:500\u2013536","journal-title":"Eur J Med Chem"},{"issue":"1","key":"2815_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1475-2875-10-263","volume":"10","author":"CA Morris","year":"2011","unstructured":"Morris CA, Duparc S, Borghini-Fuhrer I, Jung D, Shin C-S, Fleckenstein L (2011) Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration. Malar J 10(1):1\u201317","journal-title":"Malar J"},{"key":"2815_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104275","volume":"146","author":"J Nass","year":"2019","unstructured":"Nass J, Efferth T (2019) Development of artemisinin resistance in malaria therapy. Pharmacol Res 146:104275","journal-title":"Pharmacol Res"},{"issue":"8","key":"2815_CR25","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1093\/jac\/dku120","volume":"69","author":"K Patel","year":"2014","unstructured":"Patel K, Batty KT, Moore BR, Gibbons PL, Kirkpatrick CM (2014) Predicting the parasite killing effect of artemisinin combination therapy in a murine malaria model. J Antimicrob Chemother 69(8):2155\u20132163","journal-title":"J Antimicrob Chemother"},{"key":"2815_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113193","volume":"213","author":"OP Patel","year":"2021","unstructured":"Patel OP, Beteck RM, Legoabe LJ (2021) Exploration of artemisinin derivatives and synthetic peroxides in antimalarial drug discovery research. Eur J Med Chem 213:113193","journal-title":"Eur J Med Chem"},{"issue":"9","key":"2815_CR27","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.2174\/1568026616666160927160620","volume":"17","author":"MD Pedrosa","year":"2017","unstructured":"Pedrosa MD, da Cruz RMD, Viana JD, de Moura RO, Ishiki HM, Barbosa JM et al (2017) Hybrid compounds as direct multitarget ligands: a review. Curr Top Med Chem 17(9):1044\u20131049","journal-title":"Curr Top Med Chem"},{"issue":"19","key":"2815_CR28","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.3390\/molecules24193604","volume":"24","author":"S Peter","year":"2019","unstructured":"Peter S, Aderibigbe BA (2019) Ferrocene-based compounds with antimalaria\/anticancer activity. Molecules 24(19):3604","journal-title":"Molecules"},{"issue":"1","key":"2815_CR29","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/0014-4894(65)90012-3","volume":"17","author":"W Peters","year":"1965","unstructured":"Peters W (1965) Drug resistance in Plasmodium berghei Vincke and Lips, 1948. I. Chloroquine Resistance. Exp Parasitol 17(1):80\u201389","journal-title":"Exp Parasitol"},{"issue":"1","key":"2815_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-022-04115-8","volume":"21","author":"CV Plowe","year":"2022","unstructured":"Plowe CV (2022) Malaria chemoprevention and drug resistance: a review of the literature and policy implications. Malar J 21(1):1\u201325","journal-title":"Malar J"},{"issue":"11","key":"2815_CR31","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.3390\/ph14111129","volume":"14","author":"HC Quadros","year":"2021","unstructured":"Quadros HC, \u00c7apc\u0131 A, Herrmann L, D\u2019Alessandro S, Fontinha D, Azevedo R et al (2021) Studies of potency and efficacy of an optimized artemisinin-quinoline hybrid against multiple stages of the Plasmodium life cycle. Pharmaceuticals 14(11):1129","journal-title":"Pharmaceuticals"},{"issue":"1","key":"2815_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1475-2875-12-241","volume":"12","author":"T Rolling","year":"2013","unstructured":"Rolling T, Wichmann D, Schmiedel S, Burchard GD, Kluge S, Cramer JP (2013) Artesunate versus quinine in the treatment of severe imported malaria: comparative analysis of adverse events focussing on delayed haemolysis. Malar J 12(1):1\u20138","journal-title":"Malar J"},{"issue":"1","key":"2815_CR33","first-page":"9","volume":"2","author":"B Rumutsa","year":"2022","unstructured":"Rumutsa B, Nethengwe N (2022) An early warning system for malaria in Mopani district: divergent or convergent approaches. J-ICBE 2(1):9\u201312","journal-title":"J-ICBE"},{"key":"2815_CR34","doi-asserted-by":"publisher","first-page":"3013701","DOI":"10.1155\/2020\/3013701","volume":"2020","author":"S Sadeghi","year":"2020","unstructured":"Sadeghi S, Valadkhani Z, Tafreshi AS, Arjmand M, Nahravanian H, Vahabi F et al (2020) A study of synergy of combination of eosin B with chloroquine, artemisinin, and sulphadoxine-pyrimethamine on Plasmodium falciparum in vitro and Plasmodium berghei in vivo. J Trop Med 2020:3013701","journal-title":"J Trop Med"},{"issue":"2","key":"2815_CR35","doi-asserted-by":"publisher","first-page":"173","DOI":"10.30699\/ijmm.15.2.173","volume":"15","author":"A Sadeghi Tafreshi","year":"2021","unstructured":"Sadeghi Tafreshi A, Zamani Z, Sabbaghian M, Khavari-Nejad RA, Arjmand M (2021) A comparative in vitro study of the effect of eosin B on asexual blood stages and gametocyte of Plasmodium falciparum. Iran J Med Microbiol 15(2):173\u2013188","journal-title":"Iran J Med Microbiol"},{"issue":"2","key":"2815_CR36","first-page":"202","volume":"21","author":"A Tahghighi","year":"2018","unstructured":"Tahghighi A, Karimi S, Parhizgar AR, Zakeri S (2018) Synthesis and antiplasmodial activity of novel phenanthroline derivatives: an in vivo study. Iran J Basic Med Sci 21(2):202\u20132011","journal-title":"Iran J Basic Med Sci"},{"issue":"1","key":"2815_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-020-03269-7","volume":"19","author":"A Tahghighi","year":"2020","unstructured":"Tahghighi A, Mohamadi-Zarch S-M, Rahimi H, Marashiyan M, Maleki-Ravasan N, Eslamifar A (2020) In silico and in vivo anti-malarial investigation on 1-(heteroaryl)-2-((5-nitroheteroaryl) methylene) hydrazine derivatives. Malar J 19(1):1\u201312","journal-title":"Malar J"},{"issue":"3","key":"2815_CR38","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1645\/0022-3395(2005)091[0484:HMPICC]2.0.CO;2","volume":"91","author":"W Trager","year":"2005","unstructured":"Trager W, Jensen JB (2005) Human malaria parasites in continuous culture. J Parasitol 91(3):484\u2013486","journal-title":"J Parasitol"},{"key":"2815_CR39","doi-asserted-by":"crossref","unstructured":"Trevan JW (1927) The error of determination of toxicity. In:\u00a0Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character, 101(712):483\u2013514","DOI":"10.1098\/rspb.1927.0030"},{"key":"2815_CR40","unstructured":"World Health Organization (2020) Report on antimalarial drug efficacy, resistance and response: 10 years of surveillance (2010\u20132019), 19 November 2020. Geneva. https:\/\/www.who.int\/publications\/i\/item\/9789240012813"},{"key":"2815_CR41","unstructured":"World Health Organization (2021) World malaria report. Geneva. https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2021"},{"key":"2815_CR42","unstructured":"World Health Organization (2022) World malaria report, 8 December 2022, Geneva. https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2022"},{"issue":"1","key":"2815_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12936-017-1725-z","volume":"16","author":"S-J Yeo","year":"2017","unstructured":"Yeo S-J, Liu D-X, Kim HS, Park H (2017) Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria. Malar J 16(1):1\u20139","journal-title":"Malar J"},{"key":"2815_CR44","doi-asserted-by":"crossref","unstructured":"Zamani Z, Tafreshi AS, Nahrevanian H, Lame-Rad B, Pourfallah F, Eslamifar H et al (2012) Efficacy of eosin B as a new antimalarial drug in a murine model. Malar Res Treat 2012:381724","DOI":"10.1155\/2012\/381724"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-023-02815-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-023-02815-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-023-02815-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T08:04:17Z","timestamp":1716365057000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-023-02815-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,24]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["2815"],"URL":"https:\/\/doi.org\/10.1007\/s00210-023-02815-9","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,24]]},"assertion":[{"value":"18 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 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":"All applicable and acceptable guidelines for the care and use of animals were followed in the study. The research committee and institutional Ethics Committee of the Pasteur Institute of Iran approved this project.","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"}}]}}