{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:13:43Z","timestamp":1786119223316,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004167","name":"Medicines for Malaria Venture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004167","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n The roots of the climbing shrub\n Cryptolepis sanguinolenta<\/jats:italic>\n are traditionally used in West Africa for the treatment of malaria. The principal constituent, cryptolepine (\n 1<\/jats:bold>\n ), has been shown to have antimalarial activity but there are concerns regarding its toxicity on account of its DNA\u2010intercalating property. The synthetic analogue, 2,7\u2010dibromocryptolepine, (\n 2<\/jats:bold>\n ) does not intercalate into DNA and is markedly more active than the parent against\n Plasmodium<\/jats:italic>\n sp. in vitro and in vivo. The aim of this study was to carry out a pre\u2010clinical assessment of\n 1<\/jats:bold>\n and\n 2<\/jats:bold>\n , and if appropriate, carry out in vivo pharmacokinetic studies. Cryptolepine (\n 1<\/jats:bold>\n ) and 2,7\u2010dibromocryptolepine (\n 2<\/jats:bold>\n ), were evaluated in a range of in vitro assays in line with those recommended by Medicines for Malaria Venture (MMV) for the profiling of a Validated Hit Compound (\n https:\/\/www.mmv.org\/frontrunner-templates<\/jats:ext-link>\n ). In vitro profiling of\n 1<\/jats:bold>\n and\n 2<\/jats:bold>\n showed that\n 2<\/jats:bold>\n is superior to\n 1<\/jats:bold>\n with respect to antiplasmodial activities, and the parasite rate of kill (fast for\n 2<\/jats:bold>\n , in contrast with modest for\n 1<\/jats:bold>\n ); however\n 2<\/jats:bold>\n exhibited potent inhibition of the hERG potassium channel, (IC\n 50<\/jats:sub>\n \u2009=\u20091.0\u2009\u00b5M compared with 7.8\u2009\u00b5M for\n 1<\/jats:bold>\n ), raising concerns that\n 2<\/jats:bold>\n may be cardiotoxic, so that\n 2<\/jats:bold>\n was not selected for in vivo pharmacokinetic profiling. The studies of cryptolepine (\n 1<\/jats:bold>\n ) pharmacokinetics in the rat revealed a second peak, especially with oral administration, indicating that enterohepatic circulation following biliary excretion may be taking place. This study complements previous pharmacokinetic data of\n 1<\/jats:bold>\n and presents novel data on 2,7\u2010dibromocryptolepine (\n 2<\/jats:bold>\n ) that will inform the development of cryptolepine analogues as potential antimalarial agents.\n <\/jats:p>","DOI":"10.1002\/ddr.70245","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T14:45:08Z","timestamp":1770129908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antiplasmodial Activity and Pharmacokinetic Profiling of Cryptolepine and 2,7\u2010Dibromocryptolepine With a View to Informing the Design of Novel Antimalarial Cryptolepine Analogues"],"prefix":"10.1002","volume":"87","author":[{"given":"Elodie","family":"Chenu","sequence":"first","affiliation":[{"name":"MMV Medicines for Malaria Venture Meyrin Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Duffy","sequence":"additional","affiliation":[{"name":"MMV Medicines for Malaria Venture Meyrin Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold Donkor","family":"Forkuo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences Kwame Nkrumah University of Science and Technology (KNUST) Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Y.","family":"Gbedema","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences Kwame Nkrumah University of Science and Technology (KNUST) Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seham","family":"Abdelall","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3362-7558","authenticated-orcid":false,"given":"Muhammad","family":"Wahajuddin","sequence":"additional","affiliation":[{"name":"Institute of Cancer Therapeutics School of Pharmacy and Medical Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw S.","family":"Jones","sequence":"additional","affiliation":[{"name":"Institute of Cancer Therapeutics School of Pharmacy and Medical Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9815-5806","authenticated-orcid":false,"given":"Colin W.","family":"Wright","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences University of Bradford Bradford 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