{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:37:41Z","timestamp":1762144661304},"reference-count":19,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"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":[[2009,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Genzyme 644131, 8-methyl-5\u2032-{[(\n            <jats:italic>Z<\/jats:italic>\n            )-4-aminobut-2-enyl](methylamino)}adenosine, is an analog of the enzyme activated\n            <jats:italic>S<\/jats:italic>\n            -adenosylmethionine decarboxylase (AdoMetDC) inhibitor and the trypanocidal agent MDL-7381, 5-{[(\n            <jats:italic>Z<\/jats:italic>\n            )-4-aminobut-2-enyl](methylamino)}adenosine. The analog differs from the parent in having an 8-methyl group on the purine ring that bestows favorable pharmacokinetic, biochemical, and trypanocidal activities. The compound was curative in acute\n            <jats:italic>Trypanosoma brucei brucei<\/jats:italic>\n            and drug-resistant\n            <jats:italic>Trypanosoma brucei rhodesiense<\/jats:italic>\n            model infections, with single-dose activity in the 1- to 5-mg\/kg\/day daily dose range for 4 days against\n            <jats:italic>T. brucei brucei<\/jats:italic>\n            and 25- to 50-mg\/kg twice-daily dosing against\n            <jats:italic>T. brucei rhodesiense<\/jats:italic>\n            infections. The compound was not curative in the TREU 667 central nervous system model infection but cleared blood parasitemia and extended time to recrudescence in several groups. This study shows that AdoMetDC remains an attractive chemotherapeutic target in African trypanosomes and that chemical changes in AdoMetDC inhibitors can produce more favorable drug characteristics than the lead compound.\n          <\/jats:p>","DOI":"10.1128\/aac.00076-09","type":"journal-article","created":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T01:29:54Z","timestamp":1242696594000},"page":"3269-3272","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Trypanocidal Activity of 8-Methyl-5\u2032-{[(\n            <i>Z<\/i>\n            )-4-Aminobut-2-enyl]-(Methylamino)}Adenosine (Genz-644131), an Adenosylmethionine Decarboxylase Inhibitor"],"prefix":"10.1128","volume":"53","author":[{"given":"Cyrus J.","family":"Bacchi","sequence":"first","affiliation":[{"name":"Haskins Laboratory"},{"name":"Department of Biological and Health Sciences, Pace University, New York, New York 10038"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Robert H.","family":"Barker","sequence":"additional","affiliation":[{"name":"Haskins Laboratory"},{"name":"Genzyme Corp., Waltham, Massachusetts 02451"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aixa","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Haskins Laboratory"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradford","family":"Hirth","sequence":"additional","affiliation":[{"name":"Genzyme Corp., Waltham, Massachusetts 02451"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Rattendi","sequence":"additional","affiliation":[{"name":"Haskins Laboratory"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Yarlett","sequence":"additional","affiliation":[{"name":"Haskins Laboratory"},{"name":"Department of Chemistry and Physical Sciences, Pace University, New York, New York 10038"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford L.","family":"Hendrick","sequence":"additional","affiliation":[{"name":"Genzyme Corp., Waltham, Massachusetts 02451"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund","family":"Sybertz","sequence":"additional","affiliation":[{"name":"Genzyme Corp., Waltham, Massachusetts 02451"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.6.1448"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6775372"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.6.1183"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.12.2736"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01674-08"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.8.1485"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1042\/bj2740527","volume":"274","year":"1991","unstructured":"Byers, T. 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