{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:22:34Z","timestamp":1773422554285,"version":"3.50.1"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[1991,7,1]],"date-time":"1991-07-01T00:00:00Z","timestamp":678326400000},"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":[[1991,7]]},"abstract":"<jats:p>5'-Deoxy-5'-(methylthio)adenosine (MTA) is a by-product of polyamine metabolism and is phosphoryolytically cleaved to adenine and 5-deoxy-5-(methylthio)ribose-1-phosphate (MTR-1-P) by MTA phosphorylase. In eukaryotes, adenine is subsequently salvaged and converted to nucleotides, while MTR-1-P is converted to methionine. We examined 5'-deoxy-5'-substituted analogs of MTA for trypanocidal activity in vitro and in vivo. 5'-Deoxy-5'-(hydroxyethyl)thioadenosine (HETA) and its 5'-bromo,5'-chloro and 5'-fluoro derivatives were cleaved by extracts of the African trypanosome Trypanosoma brucei brucei (Km for MTA, 11.5 microM; Km for HETA, 13.2 microM) in a phosphate-dependent reaction. HETA and the three halo analogs were 50% inhibitory to growth at 0.5 to 5.0 microM in vitro. Inhibition of growth was reversible by exogenous methionine and 2-keto-4-methylthiobutyric acid, an intermediate in methionine synthesis from MTR-1-P. HETA was selected for further study in vivo. When administered by miniosmotic pump (25 to 150 mg\/kg\/day for 7 days) to mice infected with T. brucei brucei, HETA effected 70 to 90% cure rates. Results of this study indicate that these analogs of MTA are converted to trypanocidal MTR-1-P analogs and that this approach deserves further consideration in the development of novel chemotherapy of trypanosomiasis.<\/jats:p>","DOI":"10.1128\/aac.35.7.1315","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:05:50Z","timestamp":1340841950000},"page":"1315-1320","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["5'-Alkyl-substituted analogs of 5'-methylthioadenosine as trypanocides"],"prefix":"10.1128","volume":"35","author":[{"given":"C J","family":"Bacchi","sequence":"first","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J R","family":"Sufrin","sequence":"additional","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H C","family":"Nathan","sequence":"additional","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A J","family":"Spiess","sequence":"additional","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Hannan","sequence":"additional","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Garofalo","sequence":"additional","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Alecia","sequence":"additional","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Katz","sequence":"additional","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Yarlett","sequence":"additional","affiliation":[{"name":"Haskins Laboratory, Pace University, New York, New York 10038."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.35.7.1315","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.35.7.1315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T15:19:04Z","timestamp":1645456744000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.35.7.1315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,7]]},"references-count":0,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1991,7]]}},"alternative-id":["10.1128\/AAC.35.7.1315"],"URL":"https:\/\/doi.org\/10.1128\/aac.35.7.1315","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,7]]},"assertion":[{"value":"1991-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}