{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:29:46Z","timestamp":1768282186200,"version":"3.49.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2004,8,1]],"date-time":"2004-08-01T00:00:00Z","timestamp":1091318400000},"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":[[2004,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            This paper describes the design and evaluation of novel azasterols as potential compounds for the treatment of leishmaniasis and other diseases caused by trypanosomatid parasites. Azasterols are a known class of (\n            <jats:italic>S<\/jats:italic>\n            )-adenosyl-\n            <jats:sc>l<\/jats:sc>\n            -methionine: \u0394\n            <jats:sup>24<\/jats:sup>\n            -sterol methyltransferase(24-SMT) inhibitors in fungi, plants, and some parasitic protozoa. The compounds prepared showed activity at micromolar and nanomolar concentrations when tested against\n            <jats:italic>Leishmania<\/jats:italic>\n            spp. and\n            <jats:italic>Trypanosoma<\/jats:italic>\n            spp. The enzymatic and sterol composition studies indicated that the most active compounds acted by inhibiting 24-SMT. The role of the free hydroxyl group at position 3 of the sterol nucleus was also probed. When an acetate was attached to the 3\u03b2-OH, the compounds did not inhibit the enzyme but had an effect on parasite growth and the levels of sterols in the parasite, suggesting that the acetate group was removed in the organism. Thus, an acetate group on the 3\u03b2-OH may have application as a prodrug. However, there may be an additional mode(s) of action for these acetate derivatives. These compounds were shown to have ultrastructural effects on\n            <jats:italic>Leishmania amazonensis<\/jats:italic>\n            promastigote membranes, including the plasma membrane, the mitochondrial membrane, and the endoplasmic reticulum. The compounds were also found to be active against the bloodstream form (trypomastigotes) of\n            <jats:italic>Trypanosoma brucei rhodesiense<\/jats:italic>\n            , a causative agent of African trypanosomiasis.\n          <\/jats:p>","DOI":"10.1128\/aac.48.8.2937-2950.2004","type":"journal-article","created":{"date-parts":[[2004,7,23]],"date-time":"2004-07-23T18:45:20Z","timestamp":1090608320000},"page":"2937-2950","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":86,"title":["Novel Azasterols as Potential Agents for Treatment of Leishmaniasis and Trypanosomiasis"],"prefix":"10.1128","volume":"48","author":[{"given":"Silvia","family":"Orenes Lorente","sequence":"first","affiliation":[{"name":"Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliany C. F.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratorio de Ultraestrutura Celular Hertha Meyer, Instituto de Biofi\u0301sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Cie\u0302ncias da Sau\u0301de, Ilha do Funda\u0303o 21949-900, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Jime\u0301nez Jime\u0301nez","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina \u201cLo\u0301pez-Neyra,\u201d 18001 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda","family":"Joyce-Menekse","sequence":"additional","affiliation":[{"name":"Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratorio de Qui\u0301mica Biolo\u0301gica, Centro de Bioqui\u0301mica y Biofi\u0301sica, Instituto Venezolano de Investigaciones Cienti\u0301ficas, Carretera Panamericana, Caracas 1020, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon L.","family":"Croft","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Yardley","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"de Luca-Fradley","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis M.","family":"Ruiz-Pe\u0301rez","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina \u201cLo\u0301pez-Neyra,\u201d 18001 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio","family":"Urbina","sequence":"additional","affiliation":[{"name":"Laboratorio de Qui\u0301mica Biolo\u0301gica, Centro de Bioqui\u0301mica y Biofi\u0301sica, Instituto Venezolano de Investigaciones Cienti\u0301ficas, Carretera Panamericana, Caracas 1020, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanderley","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laboratorio de Ultraestrutura Celular Hertha Meyer, Instituto de Biofi\u0301sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Cie\u0302ncias da Sau\u0301de, Ilha do Funda\u0303o 21949-900, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Gonza\u0301lez Pacanowska","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologi\u0301a y Biomedicina \u201cLo\u0301pez-Neyra,\u201d 18001 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian H.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"9633","DOI":"10.1021\/bi00451a014","volume":"28","year":"1989","unstructured":"Ator, M. 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