{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:08:58Z","timestamp":1785431338380,"version":"3.56.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI177660"],"award-info":[{"award-number":["AI177660"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI152220"],"award-info":[{"award-number":["AI152220"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI153100"],"award-info":[{"award-number":["AI153100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI158533"],"award-info":[{"award-number":["AI158533"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I01BX005674"],"award-info":[{"award-number":["1I01BX005674"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH2210494"],"award-info":[{"award-number":["W81XWH2210494"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Human babesiosis is an emerging tick-borne disease caused by\n                      <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n                      parasites, most notably\n                      <jats:italic toggle=\"yes\">Babesia microti<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Babesia duncani<\/jats:italic>\n                      in North America and\n                      <jats:italic toggle=\"yes\">Babesia divergens<\/jats:italic>\n                      in Europe. Infections can be severe or persistent or relapse despite treatment, and current therapeutic options remain limited, underscoring the urgent need for new and effective treatment options. Acridone derivatives originally developed as potent antimalarial agents against multiple life cycle stages of the malaria parasites were evaluated for their antibabesial activity using continuous\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      culture systems of\n                      <jats:italic toggle=\"yes\">B. duncani<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">B. divergens<\/jats:italic>\n                      . Lead candidates were assessed for selectivity against human cell lines to establish preliminary safety profiles, and select compounds were further advanced into preliminary\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      efficacy studies using murine models of\n                      <jats:italic toggle=\"yes\">B. duncani<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">B. microti<\/jats:italic>\n                      babesiosis to assess their therapeutic potential. A set of prioritized acridone derivatives demonstrated potent\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity against both\n                      <jats:italic toggle=\"yes\">B. duncani<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">B. divergens<\/jats:italic>\n                      and displayed favorable selectivity indices relative to human cell lines. However,\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      evaluation of representative compounds did not achieve parasite clearance in murine models. Structure-activity relationship (SAR) analyses highlight key structural features that are critical for maintaining antibabesial potency and offer guidance for further lead optimization. Acridone derivatives show strong\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      antibabesial activity and represent promising lead chemotypes for therapeutic development. To advance these candidates, future studies focused on optimizing their pharmacokinetic properties and evaluating synergistic combination regimens will be essential for progressing toward effective treatments for human babesiosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00016-26","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:07:37Z","timestamp":1777280857000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating acridones as novel therapeutics for human babesiosis"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4944-6006","authenticated-orcid":true,"given":"Pratap","family":"Vydyam","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anasuya C.","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozalia A.","family":"Dodean","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00yn2fy02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Portland State University","place":["Portland, USA"]},{"id":[{"id":"https:\/\/ror.org\/01b3ys956","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterans Affairs Medical Center","place":["Portland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6381-1236","authenticated-orcid":true,"given":"Papireddy","family":"Kancharla","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00yn2fy02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Portland State University","place":["Portland, USA"]},{"id":[{"id":"https:\/\/ror.org\/01b3ys956","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterans Affairs Medical Center","place":["Portland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane X.","family":"Kelly","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00yn2fy02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Portland State University","place":["Portland, USA"]},{"id":[{"id":"https:\/\/ror.org\/01b3ys956","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterans Affairs Medical Center","place":["Portland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5028-1400","authenticated-orcid":true,"given":"Choukri","family":"Ben Mamoun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine","place":["New Haven, USA"]},{"name":"Department of Microbial Pathogenesis, Yale School of Medicine","place":["New Haven, USA"]},{"name":"Department of Pathology, Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1216"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2023.03.013"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2018.11.007"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-124-7-199604010-00004"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11060947"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1004.030377"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2008.03.010"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10091120"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/525852"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2015.02.008"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/649859"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix477"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00423-24"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad315"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01961"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00419"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00539"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac181"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.4549"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01360-8"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2024.2386136"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151519"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00662-21"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab321"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00035-25"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.AC118.005771"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","unstructured":"Kancharla P Dodean RA Li Y Zhang X Kelly S Charlton J Binauhan A Garcia L Caridha D Madejczyk MS et al.. 2025. Potent acridone antimalarial against all three life stages of Plasmodium. Res Sq:rs.3.rs-6858328. doi:10.21203\/rs.3.rs-6858328\/v1","DOI":"10.21203\/rs.3.rs-6858328\/v1"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.1c00016"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00016-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00016-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:03:30Z","timestamp":1781787810000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00016-26"}},"subtitle":[],"editor":[{"given":"Audrey","family":"Odom John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,3]]}},"alternative-id":["10.1128\/aac.00016-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00016-26","relation":{"has-preprint":[{"id-type":"doi","id":"10.64898\/2026.01.07.698299","asserted-by":"object"}]},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"2026-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00016-26"}}