{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:15:24Z","timestamp":1788225324107,"version":"build-2803163510"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["2023ACB206047"],"award-info":[{"award-number":["2023ACB206047"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["20242BAB20466"],"award-info":[{"award-number":["20242BAB20466"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["20242BAB25549"],"award-info":[{"award-number":["20242BAB25549"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21867001"],"award-info":[{"award-number":["21867001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22167002"],"award-info":[{"award-number":["22167002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22467001"],"award-info":[{"award-number":["22467001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360675"],"award-info":[{"award-number":["82360675"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Double-Thousand Talents Plan of Jiangxi Province","award":["jxsq2019201025"],"award-info":[{"award-number":["jxsq2019201025"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Millions of people in tropical and subtropical regions rely on praziquantel to treat schistosomiasis. The limitations of current treatments and the emerging risk of praziquantel resistance highlight an urgent need for new chemotherapeutic agents. Here, we report the discovery of a novel series of\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -aryl-\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      \u2032-methylbenzohydrazides exhibiting potent activity against\n                      <jats:italic toggle=\"yes\">Schistosoma japonicum<\/jats:italic>\n                      (Chinese strain). Among these, compound 41 demonstrated potent\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity against adult\n                      <jats:italic toggle=\"yes\">S. japonicum<\/jats:italic>\n                      , with an LC\n                      <jats:sub>50<\/jats:sub>\n                      (72 h) value of 61.40 \u00b1 1.80 \u03bcM. Ultrastructural analysis revealed that this lead compound induced tegumental disruption mechanistically comparable to praziquantel, manifested through syncytial layer disintegration, subtegumental musculature exposure, and pronounced contraction of both oral and ventral suckers. In murine schistosomiasis models, oral administration of compound 18 achieved a significant 40% worm burden reduction against juvenile-stage worms, while compound 5 demonstrated a 34% reduction against adult-stage worms.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      therapeutic assessments confirmed that compounds 5, 18, and 41 ameliorated hepatic pathology. Notably, mice administered compound 18 during juvenile worm development displayed significantly reduced egg burdens. Toxicological profiling indicated transient nephrotoxicity associated with compound 18 during juvenile-stage treatment, whereas compounds 5 and 41 exhibited favorable safety profiles across all developmental stages without observable nephrotoxicity. Acute oral toxicity studies confirmed low acute toxicity for all three candidates. The combined schistosomicidal efficacy, organ-protective effects, and superior safety profile of compound 5 position it as a highly promising lead candidate for further preclinical development. This chemotype provides a robust foundation for novel antischistosomal drug discovery in the post-praziquantel era.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      With praziquantel (PZQ) as the sole therapeutic option for schistosomiasis, emerging drug resistance underscores the critical need for new agents. We identified a novel series of\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -aryl-\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      \u2032-methylbenzohydrazides with potent activity against\n                      <jats:italic toggle=\"yes\">Schistosoma japonicum<\/jats:italic>\n                      . Lead compound 41 showed significant\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      efficacy (LC\n                      <jats:sub>50<\/jats:sub>\n                      = 61.40 \u00b1 1.80 \u03bcM) and induced tegumental disruption similar to PZQ. In murine models, compounds 18 and 5 reduced juvenile and adult worm burdens by 40% and 34%, respectively, and alleviated hepatic pathology. Compound 5 exhibited a favorable safety profile without nephrotoxicity. With its potent schistosomicidal activity, organ protection, and low toxicity, compound 5 represents a promising lead compound for preclinical development, offering a new chemotype for post-PZQ drug discovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01932-25","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:01:01Z","timestamp":1765893661000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Discovery and biological evaluation of novel\n                    <i>N<\/i>\n                    -aryl-\n                    <i>N<\/i>\n                    \u2032-methylbenzodrazides against\n                    <i>Schistosoma japonicum in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7916-9890","authenticated-orcid":true,"given":"Lvyin","family":"Zheng","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jf7e446","id-type":"ROR","asserted-by":"publisher"}],"name":"Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, Gannan Normal University","place":["Ganzhou, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Zhong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jf7e446","id-type":"ROR","asserted-by":"publisher"}],"name":"Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, Gannan Normal University","place":["Ganzhou, People's Republic of 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