{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:27:35Z","timestamp":1790868455225,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Arylimidamides (AIAs) represent a new class of molecules that exhibit potent antileishmanial activity (50% inhibitory concentration [IC\n            <jats:sub>50<\/jats:sub>\n            ], &lt;1 \u03bcM) against both\n            <jats:italic>Leishmania donovani<\/jats:italic>\n            axenic amastigotes and intracellular\n            <jats:italic>Leishmania<\/jats:italic>\n            , the causative agent for human visceral leishmaniasis (VL). A systematic lead discovery program was employed to characterize\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            antileishmanial activities, pharmacokinetics, mutagenicities, and toxicities of two novel AIAs, DB745 and DB766. They were exceptionally active (IC\n            <jats:sub>50<\/jats:sub>\n            \u2264 0.12 \u03bcM) against intracellular\n            <jats:italic>L. donovani<\/jats:italic>\n            ,\n            <jats:italic>Leishmania amazonensis<\/jats:italic>\n            , and\n            <jats:italic>Leishmania major<\/jats:italic>\n            and did not exhibit mutagenicity in an Ames screen. DB745 and DB766, given orally, produced a dose-dependent inhibition of liver parasitemia in two efficacy models,\n            <jats:italic>L. donovani<\/jats:italic>\n            -infected mice and hamsters. Most notably, DB766 (100 mg\/kg of body weight\/day for 5 days) reduced liver parasitemia in mice and hamsters by 71% and 89%, respectively. Marked reduction of parasitemia in the spleen (79%) and bone marrow (92%) of hamsters was also observed. Furthermore, these compounds distributed to target tissues (liver and spleen) and had a moderate oral bioavailability (up to 25%), a large volume of distribution, and an elimination half-life ranging from 1 to 2 days in mice. In a repeat-dose toxicity study of mice, there was no indication of liver or kidney toxicity for DB766 from serum chemistries, although mild hepatic cell eosinophilia, hypertrophy, and fatty changes were noted. These results demonstrated that arylimidamides are a promising class of molecules that possess good antileishmanial activity and desirable pharmacokinetics and should be considered for further preclinical development as an oral treatment for VL.\n          <\/jats:p>","DOI":"10.1128\/aac.00250-10","type":"journal-article","created":{"date-parts":[[2010,4,6]],"date-time":"2010-04-06T00:27:25Z","timestamp":1270513645000},"page":"2507-2516","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["Novel Arylimidamides for Treatment of Visceral Leishmaniasis"],"prefix":"10.1128","volume":"54","author":[{"given":"Michael Zhuo","family":"Wang","sequence":"first","affiliation":[{"name":"Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Mark","family":"Sweat","sequence":"additional","affiliation":[{"name":"Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trupti","family":"Pandharkar","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad E.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Physics, Augusta State University, Augusta, Georgia 30904"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed","family":"Riccio","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toufan","family":"Parman","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Munde","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Georgia State University, Atlanta, Georgia 30302"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Mandal","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rentala","family":"Madhubala","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Tidwell","sequence":"additional","affiliation":[{"name":"Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599"},{"name":"Department of Pathology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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