{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:30:17Z","timestamp":1791322217054,"version":"4.3.1"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T00:00:00Z","timestamp":1389139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    is responsible of the most severe form of malaria, and new targets and novel chemotherapeutic scaffolds are needed to fight emerging multidrug\u2010resistant strains of this parasite. Bis\u2010alkylguanidines have been designed to mimic choline, resulting in the inhibition of plasmodial de\u2005novo phosphatidylcholine biosynthesis. Despite potent in vitro antiplasmodial and in vivo antimalarial activities, a major drawback of these compounds for further clinical development is their low oral bioavailability. To solve this issue, various modulations were performed on bis\u2010alkylguanidines. The introduction of N\u2010disubstituents on the guanidino motif improved both in vitro and in vivo activities. On the other hand, in vivo pharmacological evaluation in a mouse model showed that the\n                    <jats:italic>N<\/jats:italic>\n                    \u2010hydroxylated derivatives constitute the first oral bioprecursors in bis\u2010alkylguanidine series. This study paves the way for bis\u2010alkylguanidine\u2010based oral antimalarial agents targeting plasmodial phospholipid metabolism.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.201300419","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T16:43:15Z","timestamp":1389199395000},"page":"300-304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Development of the First Oral Bioprecursors of Bis\u2010alkylguanidine Antimalarial Drugs"],"prefix":"10.1002","volume":"9","author":[{"given":"M\u00e9lissa","family":"Degardin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Wein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Fr\u00e9d\u00e9ric","family":"Duckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Maynadier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Guy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Durand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Escale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Vial","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen","family":"Vo\u2010Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,8]]},"reference":[{"key":"e_1_2_4_1_2","unstructured":"World Malaria Report 2012 World Health Organization Geneva (Switzerland) 2012;http:\/\/www.who.int\/malaria\/publications\/world_malaria_report_2012\/en(Accessed: December 16 2013)."},{"key":"e_1_2_4_2_2","unstructured":"Global Report on Antimalarial Efficacy and Drug Resistance 2000\u20132010 World Health Organization Geneva (Switzerland) 2010;http:\/\/www.who.int\/malaria\/publications\/atoz\/9789241500470\/en\/index.html(Accessed: December 16 2013)."},{"key":"e_1_2_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61963-0"},{"key":"e_1_2_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_2_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70226-8"},{"key":"e_1_2_4_6_2","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-111-6:347"},{"key":"e_1_2_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/9783527633883.ch8"},{"key":"e_1_2_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067236"},{"key":"e_1_2_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404037101"},{"key":"e_1_2_4_10_2","unstructured":"H.Vial M.Calas R.Escale V.Vidal F.Bressolle M. 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