{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:44:23Z","timestamp":1791877463992,"version":"4.3.4"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01 AI150763"],"award-info":[{"award-number":["R01 AI150763"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007500","name":"Bloomberg Family Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007500","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JHSPH | Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,1,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The antimalarial quinolines pyronaridine and chloroquine both inhibit hemozoin crystallization, predominately produced by\n              <jats:italic>Plasmodium falciparum<\/jats:italic>\n              intra-erythrocytic trophozoite stage parasites. Pyronaridine extends activity to ring-stage chloroquine-sensitive parasites, in contrast to chloroquine. Here, we investigated chloroquine and pyronaridine hemozoin inhibition type correlated to stage-specific activity on chloroquine-resistant ring-stage artemisinin sensitive and resistant\n              <jats:italic>P. falciparum<\/jats:italic>\n              CamWT and CamWT-C580Y parasites. Pyronaridine (2.8 \u03bcM) is tenfold more potent at beta-hematin nucleation than chloroquine (40 \u03bcM). Both pyronaridine and chloroquine (0.2 and 0.7 \u03bcM, respectively) had similar sub-\u03bcM inhibition of beta-hematin extension.\n              <jats:italic>P. falciparum<\/jats:italic>\n              CamWT-C580Y parasites produce smaller width hemozoin crystals which extend less than isogenic CamWT hemozoin. Stage-specific pulse dose pyronaridine and chloroquine on CamWT-C580Y or CamWT isogenic parasites observed 3- to 4-fold higher pyronaridine IC\n              <jats:sub>50<\/jats:sub>\n              s compared to 10- to 15-fold higher chloroquine on most CamWT-C580Y to CamWT stages. These findings collectively show that hemozoin nucleation inhibition widens stage-specific pyronaridine activity on\n              <jats:italic>P. falciparum<\/jats:italic>\n              drug-resistant parasites.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01208-24","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T14:03:15Z","timestamp":1734012195000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Stage-specific pharmacodynamic chloroquine and pyronaridine action on artemisinin ring-stage resistant Kelch C580Y mutation\n            <i>Plasmodium falciparum<\/i>\n            correlates to hemozoin inhibition process"],"prefix":"10.1128","volume":"69","author":[{"given":"Abeer","family":"Sayeed","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revie","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Vekilov","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of Houston","place":["Houston, USA"]},{"name":"Department of Chemistry, University of Houston","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Rimer","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of Houston","place":["Houston, USA"]},{"name":"Department of Chemistry, University of Houston","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0319-0578","authenticated-orcid":true,"given":"David J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01636-09"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3189"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14412"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00197-15"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.8b00959"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-023-06024-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217452110"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.178830"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0539-5"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2021.09.005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-29088-5_12"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1988.38.30"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00119-06"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060986"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2003.08.009"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05046-z"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00394-18"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211803"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.16.6.710"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01208-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01208-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T14:04:39Z","timestamp":1738332279000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01208-24"}},"subtitle":[],"editor":[{"given":"Audrey","family":"Odom 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