{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T17:21:41Z","timestamp":1764350501072,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["IP-2014-09-1501, IP-2013-5660","Young researcher\u2019s career development project \u2013 training of doctoral students"],"award-info":[{"award-number":["IP-2014-09-1501, IP-2013-5660","Young researcher\u2019s career development project \u2013 training of doctoral students"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["Stimulus of Scientific Employement 2018"],"award-info":[{"award-number":["Stimulus of Scientific Employement 2018"]}]},{"DOI":"10.13039\/100008993","name":"University of Zagreb","doi-asserted-by":"publisher","award":["support for 2018"],"award-info":[{"award-number":["support for 2018"]}],"id":[{"id":"10.13039\/100008993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This paper describes a continuation of our efforts in the pursuit of novel antiplasmodial agents with optimized properties. Following our previous discovery of biologically potent asymmetric primaquine (PQ) and halogenaniline fumardiamides (1\u20136), we now report their significant in vitro activity against the hepatic stages of Plasmodium parasites. Furthermore, we successfully prepared chloroquine (CQ) analogue derivatives (11\u201316) and evaluated their activity against both the hepatic and erythrocytic stages of Plasmodium. Our results have shown that PQ fumardiamides (1\u20136) exert both higher activity against P. berghei hepatic stages and lower toxicity against human hepatoma cells than the parent drug and CQ derivatives (11\u201316). The favourable cytotoxicity profile of the most active compounds, 5 and 6, was corroborated by assays performed on human cells (human breast adenocarcinoma (MCF-7) and non-tumour embryonic kidney cells (HEK293T)), even when glucose-6-phosphate dehydrogenase (G6PD) was inhibited. The activity of CQ fumardiamides on P. falciparum erythrocytic stages was higher than that of PQ derivatives, comparable to CQ against CQ-resistant strain PfDd2, but lower than CQ when tested on the CQ-sensitive strain Pf3D7. In addition, both sets of compounds showed favourable drug-like properties. Hence, quinoline fumardiamides could serve as a starting point towards the development of safer and more effective antiplasmodial agents.<\/jats:p>","DOI":"10.3390\/molecules24152812","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T11:39:37Z","timestamp":1564659577000},"page":"2812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Primaquine and Chloroquine Fumardiamides as Promising Antiplasmodial Agents"],"prefix":"10.3390","volume":"24","author":[{"given":"Maja","family":"Beus","sequence":"first","affiliation":[{"name":"University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, HR-10 000 Zagreb, Croatia"}]},{"given":"Diana","family":"Fontinha","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal"}]},{"given":"Jana","family":"Held","sequence":"additional","affiliation":[{"name":"University of T\u00fcbingen, Institute of Tropical Medicine, Wilhelmstra\u00dfe 27, 72074 T\u00fcbingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-1116","authenticated-orcid":false,"given":"Zrinka","family":"Raji\u0107","sequence":"additional","affiliation":[{"name":"University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, HR-10 000 Zagreb, Croatia"}]},{"given":"Lidija","family":"Uzelac","sequence":"additional","affiliation":[{"name":"Rudjer Bo\u0161kovi\u0107 Institute, Division of Molecular Medicine, Laboratory of Experimental Therapy, 10 000 Zagreb, Croatia"}]},{"given":"Marijeta","family":"Kralj","sequence":"additional","affiliation":[{"name":"Rudjer Bo\u0161kovi\u0107 Institute, Division of Molecular Medicine, Laboratory of Experimental Therapy, 10 000 Zagreb, Croatia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1746-6029","authenticated-orcid":false,"given":"Miguel","family":"Prud\u00eancio","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4355-8816","authenticated-orcid":false,"given":"Branka","family":"Zorc","sequence":"additional","affiliation":[{"name":"University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, HR-10 000 Zagreb, Croatia"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018). World Malaria Report 2018, World Health Organization."},{"key":"ref_2","unstructured":"World Health Organization (2015). Global Technical Strategy for Malaria 2016\u20132030, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nrmicro1529","article-title":"The silent path to thousands of merozoites: The Plasmodium liver stage","volume":"4","author":"Rodriguez","year":"2006","journal-title":"Nat. Rev. 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