{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:03:44Z","timestamp":1782281024693,"version":"3.54.5"},"posted":{"date-parts":[[2026,1,8]]},"group-title":"Microbiology","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Human babesiosis is an emerging tick-borne disease caused by\n                    <jats:italic>Babesia<\/jats:italic>\n                    parasites, most notably\n                    <jats:italic>Babesia microti<\/jats:italic>\n                    and\n                    <jats:italic>Babesia duncani<\/jats:italic>\n                    in North America and\n                    <jats:italic>Babesia divergens<\/jats:italic>\n                    in Europe. Infections can be severe, persistent, or relapse despite treatment, and current therapeutic options remain limited, underscoring the urgent need for new and effective treatment options.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    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>in vitro<\/jats:italic>\n                    culture systems of\n                    <jats:italic>B. duncani<\/jats:italic>\n                    and\n                    <jats:italic>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>in vivo<\/jats:italic>\n                    efficacy studies using murine models of\n                    <jats:italic>B. duncani<\/jats:italic>\n                    and\n                    <jats:italic>B. microti<\/jats:italic>\n                    babesiosis to assess their therapeutic potential.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Nine prioritized acridone derivatives demonstrated potent\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity against both\n                    <jats:italic>B. duncani<\/jats:italic>\n                    and\n                    <jats:italic>B. divergens<\/jats:italic>\n                    , accompanied by favorable selectivity indices relative to human cell lines. However,\n                    <jats:italic>in vivo<\/jats:italic>\n                    evaluation of representative compounds did not achieve parasite clearance in murine models. Structure-activity relationship (SAR) analyses highlighted key structural features that are critical for maintaining antibabesial potency and offer guidance for further lead optimization.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Acridone derivatives show strong\n                    <jats:italic>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, improving in vivo efficacy, and evaluating synergistic combination regimens will be essential for progressing toward effective treatments for human babesiosis.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.07.698299","type":"posted-content","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T02:25:22Z","timestamp":1767925522000},"source":"Crossref","is-referenced-by-count":0,"title":["Evaluating Acridones as Novel Therapeutics for Human Babesiosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4944-6006","authenticated-orcid":false,"given":"Pratap","family":"Vydyam","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases New Haven, Connecticut-06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases New Haven, Connecticut-06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anasuya C.","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases New Haven, Connecticut-06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozalia A.","family":"Dodean","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Portland State University, Portland, Oregon-97201, USA"},{"name":"Department of Veterans Affairs Medical Center, Portland, Oregon-97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6381-1236","authenticated-orcid":false,"given":"Papireddy","family":"Kancharla","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Portland State University, Portland, Oregon-97201, USA"},{"name":"Department of Veterans Affairs Medical Center, Portland, Oregon-97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane X.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Portland State University, Portland, Oregon-97201, USA"},{"name":"Department of Veterans Affairs Medical Center, Portland, Oregon-97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5028-1400","authenticated-orcid":false,"given":"Choukri","family":"Ben Mamoun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases New Haven, Connecticut-06520, USA"},{"name":"Department of Microbial Pathogenesis, New Haven, Connecticut-06520, USA"},{"name":"Department of Pathology, Yale School of Medicine, New Haven, Connecticut-06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026011006250458000_2026.01.07.698299v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1216"},{"key":"2026011006250458000_2026.01.07.698299v1.2","doi-asserted-by":"crossref","unstructured":"Swanson M, P.A. , Williamson J , Montgomery S. , Trends in Reported Babesiosis Cases \u2014 United States, 2011\u20132019. 2023.","DOI":"10.1016\/j.ajt.2023.03.013"},{"key":"2026011006250458000_2026.01.07.698299v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2018.11.007"},{"key":"2026011006250458000_2026.01.07.698299v1.4","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-124-7-199604010-00004"},{"key":"2026011006250458000_2026.01.07.698299v1.5","doi-asserted-by":"crossref","unstructured":"Scott, J.D. , et al., Detection of Babesia odocoilei in Humans with Babesiosis Symptoms. 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