{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:01:18Z","timestamp":1793145678564,"version":"4.5.0"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"10","funder":[{"DOI":"10.13039\/501100019540","name":"Zhejiang Provincial Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["LR15B020001"],"award-info":[{"award-number":["LR15B020001"]}],"id":[{"id":"10.13039\/501100019540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2017YFE0102200"],"award-info":[{"award-number":["2017YFE0102200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["MC"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n<jats:title>Background:<\/jats:title>\n<jats:p> Malaria is one of the most devastating parasitic diseases, yet the discovery\nof antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed\nin the past 50 years, while the emergence of drug-resistance continues to appear.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective:<\/jats:title>\n<jats:p>This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3-\ncinnamamido-N-substituted benzamides.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>In this study, a screening of our compound library was carried out against the multidrugsensitive\nPlasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and\ntested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds\nwas evaluated using the method of Peters\u2019 4-day suppressive test.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton\nshowed moderate antimalarial activity (IC<jats:sub>50<\/jats:sub> = 1.20 \u03bcM) for the first time. A series of derivatives\nwere then synthesized through a simple four-step workflow, and half of them exhibited slightly better\nantimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds\n11, 23, 30 and 31 displayed potent activity with IC<jats:sub>50<\/jats:sub> values of approximately 0.1 \u03bcM, and\nweak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective,\nwhich might be ascribed to the poor solubility of these compounds.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p> In this study, the phenotypic screen of our compound library resulted in the first report\nof a 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and\nsynthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited\nthe most potent and selective activity against the P. falciparum 3D7 strain with IC50 values\naround 0.1 \u03bcM. Our work herein sets another example of phenotypic screen-based drug discovery,\nleading to potentially promising candidates of novel antimalarial agents once given further optimization.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1573406416666200817160708","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T08:08:42Z","timestamp":1597738122000},"page":"1207-1218","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery of 3-Cinnamamido-N-Substituted Benzamides as Potential Antimalarial Agents"],"prefix":"10.2174","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-8936","authenticated-orcid":true,"given":"Haicheng","family":"Liu","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-6944","authenticated-orcid":true,"given":"Yushi","family":"Futamura","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4581-7463","authenticated-orcid":true,"given":"Honghai","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4703-8834","authenticated-orcid":true,"given":"Aki","family":"Ishiyama","sequence":"additional","affiliation":[{"name":"Research Center for Tropical Diseases, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato- ku, Tokyo 108-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6227-8361","authenticated-orcid":true,"given":"Taotao","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5580-4212","authenticated-orcid":true,"given":"Tao","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5331-540X","authenticated-orcid":true,"given":"Qunxiong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Zhejiang Gongshang University, Hangzhou 310035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8373-4314","authenticated-orcid":true,"given":"Masato","family":"Iwatsuki","sequence":"additional","affiliation":[{"name":"Research Center for Tropical Diseases, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato- ku, Tokyo 108-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-2520","authenticated-orcid":true,"given":"Satoshi","family":"\u014cmura","sequence":"additional","affiliation":[{"name":"Research Center for Tropical Diseases, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato- ku, Tokyo 108-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6784-2737","authenticated-orcid":true,"given":"Hongbin","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3606-4925","authenticated-orcid":true,"given":"Hiroyuki","family":"Osada","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","container-title":["Medicinal 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