{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T22:56:02Z","timestamp":1775170562466,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002873","name":"Chulalongkorn University","doi-asserted-by":"publisher","award":["90th anniversary of Chulalongkorn University fund (Ratchadaphiseksomphot endowment fund)"],"award-info":[{"award-number":["90th anniversary of Chulalongkorn University fund (Ratchadaphiseksomphot endowment fund)"]}],"id":[{"id":"10.13039\/501100002873","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Thailand Graduate Institute of 529 Science and Technology (TGIST) scholarship","award":["SCA-CO-2562-9780-TH"],"award-info":[{"award-number":["SCA-CO-2562-9780-TH"]}]},{"name":"National Science and Technology Development Agency scholarship and National Science and Technology Development Agency Grant","award":["P1750501"],"award-info":[{"award-number":["P1750501"]}]},{"name":"National Science and Technology Development Agency scholarship and National Science and Technology Development Agency Grant","award":["P1850116"],"award-info":[{"award-number":["P1850116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The rapid emergence of drug resistance to the current antimalarial agents has led to the urgent need for the discovery of new and effective compounds. In this work, a series of 5-phenoxy primaquine analogs with 8-aminoquinoline core (7a\u20137h) was synthesized and investigated for their antimalarial activity against Plasmodium falciparum. Most analogs showed improved blood antimalarial activity compared to the original primaquine. To further explore a drug hybrid strategy, a conjugate compound between tetraoxane and the representative 5-phenoxy-primaquine analog 7a was synthesized. In our work, the hybrid compound 12 exhibited almost a 30-fold increase in the blood antimalarial activity (IC50 = 0.38 \u00b1 0.11 \u03bcM) compared to that of primaquine, with relatively low toxicity against mammalian cells (SI = 45.61). Furthermore, we found that these 5-phenoxy primaquine analogs and the hybrid exhibit significant heme polymerization inhibition, an activity similar to that of chloroquine, which could contribute to their improved antimalarial activity. The 5-phenoxy primaquine analogs and the tetraoxane hybrid could serve as promising candidates for the further development of antimalarial agents.<\/jats:p>","DOI":"10.3390\/molecules26133991","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T02:16:34Z","timestamp":1625019394000},"page":"3991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["5-Phenoxy Primaquine Analogs and the Tetraoxane Hybrid as Antimalarial Agents"],"prefix":"10.3390","volume":"26","author":[{"given":"Somruedee","family":"Jansongsaeng","sequence":"first","affiliation":[{"name":"Centre of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nitipol","family":"Srimongkolpithak","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutharat","family":"Pengon","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumalee","family":"Kamchonwongpaisan","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7236-0625","authenticated-orcid":false,"given":"Tanatorn","family":"Khotavivattana","sequence":"additional","affiliation":[{"name":"Centre of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"ref_1","unstructured":"(2019). 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