{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:22:58Z","timestamp":1759134178823,"version":"3.37.3"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2300800","2021YFC2300801","2021YFC2300802"],"award-info":[{"award-number":["2021YFC2300800","2021YFC2300801","2021YFC2300802"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072307"],"award-info":[{"award-number":["82072307"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The efficacy of current drugs against hookworms at a single dose is highly variable across regions, age groups and infection intensity. Extensive and repeated use of these drugs also leads to potential drug resistance. Therefore, novel drugs are required for sustained disease control.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Novel aromatic heterocycle substituted aminamidine derivatives (AADs) were synthesized based on tribendimine (TBD), and their in vivo potency against Necator americanus was tested.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The efficacy of the AADs was tested in male hamsters. Oral and IV pharmacokinetic parameters were determined in male Sprague-Dawley rats. The proteomic profiles of N. americanus samples treated with AADs were compared using tandem mass tag-based quantitative proteomic analyses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Most AADs exhibited better anthelmintic activity than TBD at a single oral dose. Compound 3c exhibited improved solubility (&amp;gt;50\u00d7), and the curative dose was as low as 25\u2005mg\/kg. Similar to TBD, 3c was rapidly metabolized after oral administration and transformed into p-(1-dimethylamino ethylimino)aniline (dADT), an active metabolite against intestinal nematodes. dADT from 3c had better pharmacokinetic profiles than that from TBD and achieved an oral bioavailability of 99.5%. Compound 3c possessed rapid anthelmintic activity, clearing all worms within 24 h after an oral dose of 50\u2005mg\/kg. Quantitative proteomic analysis indicated that it might be related to ATP metabolism and cuticle protein synthesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Compound 3c is a novel and promising compound against N. americanus in vivo.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae149","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T09:09:50Z","timestamp":1716887390000},"page":"1606-1613","source":"Crossref","is-referenced-by-count":1,"title":["The effect of novel aromatic heterocycle substituted aminamidine derivatives on <i>Necator americanus<\/i>"],"prefix":"10.1093","volume":"79","author":[{"given":"Lele","family":"Huo","sequence":"first","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases , Shanghai 200025 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufen","family":"Wei","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases , Shanghai 200025 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Xue","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases , Shanghai 200025 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases , Shanghai 200025 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Yin","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases , Shanghai 200025 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Tao","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases , Shanghai 200025 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haobing","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases , Shanghai 200025 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4386-6624","authenticated-orcid":false,"given":"Yujuan","family":"Shen","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases , Shanghai 200025 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"2024082310382489200_dkae149-B1","doi-asserted-by":"crossref","first-page":"e0011496","DOI":"10.1371\/journal.pntd.0011496","article-title":"Soil-transmitted helminths: a critical review of the impact of co-infections and implications for control and elimination","volume":"17","author":"Lebu","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"key":"2024082310382489200_dkae149-B2","doi-asserted-by":"crossref","first-page":"16088","DOI":"10.1038\/nrdp.2016.88","article-title":"Hookworm 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