{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:39:50Z","timestamp":1790239190540,"version":"4.1.0"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2000,12,1]],"date-time":"2000-12-01T00:00:00Z","timestamp":975628800000},"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":[[2000,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Sordarin derivatives represent a new class of antifungal agents that act as potent inhibitors of fungal protein synthesis and possess a broad spectrum of activity. The in vivo activity of GM193663 and GM237354 was studied in mouse models of disseminated candidiasis and aspergillosis and in a rat model of pneumocystosis. The pharmacokinetic behavior of both sordarin derivatives was studied in mice and rats. In all studies, compounds were administered by the subcutaneous route. After a subcutaneous dose of 50 mg\/kg of body weight to mice, the maximum level in serum, area under the concentration-time curve, half-life, and clearance for GM193663 and GM237354 were 51.8 and 23 \u03bcg\/ml, 79.5 and 46 \u03bcg \u00b7 h\/ml, 0.8 and 0.85 h, and 21 and 25 ml\/h, respectively. Systemic candidiasis and aspergillosis were established in CD-1 male mice infected with\n            <jats:italic>Candida albicans<\/jats:italic>\n            or\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            . For systemic candidiasis, compounds were given three times per day for seven consecutive days at 15, 30, 60, or 120 mg\/kg\/day. GM193663 and GM237354 showed dose-related efficacy against\n            <jats:italic>C. albicans<\/jats:italic>\n            , with 50% effective doses, 1 month after infection, of 25.2 and 10.7 mg\/kg\/dose, respectively. In experimental infections with\n            <jats:italic>A. fumigatus<\/jats:italic>\n            , GM237354 was given three times per day at 30, 60, or 120 mg\/kg\/day for five consecutive days. Animals treated with GM237354 demonstrated irregular responses. The survival of animals treated with GM237354 was 0, 30, and 0% at 30, 60, and 120 mg\/kg\/day, respectively. The therapeutic efficacy of GM193663 and GM237354 against\n            <jats:italic>Pneumocystis carinii<\/jats:italic>\n            was studied in an experimental\n            <jats:italic>P. carinii<\/jats:italic>\n            pneumonia (PCP) rat model. After a subcutaneous dose of 10 mg\/kg given to rats, the maximum level in serum, area under the concentration-time curve, half-life, and clearance for GM193663 and GM237354 were 6.6 and 7.2 \u03bcg\/ml, 8.5 and 11.8 \u03bcg \u00b7 h\/ml, 0.7 and 0.8 h, and 230 and 133 ml\/h, respectively. To induce spontaneous PCP, rats were chronically immunosuppressed with dexamethasone. Infected animals were treated twice daily for 10 days at 0.2, 2, or 10 mg\/kg\/day. The therapeutic effect was estimated by the reduction in the number of cysts in the lungs of treated versus untreated animals. GM193663 and GM237354 significantly reduced the mean (\u00b1 standard deviation) log number of cysts from 7.6 \u00b1 0.2 in the untreated group to 4.7 \u00b1 0.2 and 4.6 \u00b1 0.1, respectively, when the drugs were administered at a dose of 2 mg\/kg\/day. The log number of cysts was also reduced in infected animals given lower doses of the compounds (0.2 mg\/kg\/day). In summary, GM193663 and GM237354 are new sordarin derivatives that may potentially play a major role in the treatment of candidiasis and PCP. Further testing with\n            <jats:italic>Aspergillus<\/jats:italic>\n            in other animal models is warranted.\n          <\/jats:p>","DOI":"10.1128\/aac.44.12.3389-3394.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"3389-3394","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Activities of Sordarins in Experimental Models of Candidiasis, Aspergillosis, and Pneumocystosis"],"prefix":"10.1128","volume":"44","author":[{"given":"Antonio","family":"Martinez","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Research Department, Glaxo Wellcome S.A., 28760 Tres Cantos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Aviles","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Research Department, Glaxo Wellcome S.A., 28760 Tres Cantos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Jimenez","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Research Department, Glaxo Wellcome S.A., 28760 Tres Cantos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Caballero","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Research Department, Glaxo Wellcome S.A., 28760 Tres Cantos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domingo","family":"Gargallo-Viola","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Research Department, Glaxo Wellcome S.A., 28760 Tres Cantos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1997.tb05765.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/40.6.779"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.5.1284-1290.2000"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.5.1317"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.8.1811"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.10.2694"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1874-1877.2000"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/513943"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/12.6.1147"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2274"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2279"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.32.3.289"},{"key":"e_1_3_2_14_2","first-page":"12","article-title":"The problem of azole resistance in candida.","volume":"6","author":"Dupont B.","year":"1996","unstructured":"Dupont B. Dromer F. Improvisi L. The problem of azole resistance in candida. J. Mycol. Med. 6 1996 12 19","journal-title":"J. Mycol. Med."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.5.995"},{"key":"e_1_3_2_16_2","first-page":"297","article-title":"Sordarins as antifungical compounds.","volume":"1","author":"Gargallo-Viola D.","year":"1999","unstructured":"Gargallo-Viola D. Sordarins as antifungical compounds. Curr. Opin. Anti-Infect. Invest. Drugs 1 1999 297 305","journal-title":"Curr. Opin. Anti-Infect. Invest. Drugs"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.2.279"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.7.1716"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.11.2863"},{"key":"e_1_3_2_20_2","first-page":"243","article-title":"Tail sectioning: a rapid and simple method for repeated blood sampling of the rat for cortisone determination.","volume":"46","author":"Liu J.","year":"1996","unstructured":"Liu J. Vadgama J. Diaz T. Henry J. P. Tail sectioning: a rapid and simple method for repeated blood sampling of the rat for cortisone determination. Lab. Anim. Sci. 46 1996 243 245","journal-title":"Lab. Anim. Sci."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.2307\/3283134"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/313756"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/40.6.753"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001340050552"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.12.3389-3394.2000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.12.3389-3394.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:23:04Z","timestamp":1645460584000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.44.12.3389-3394.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12]]},"references-count":23,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2000,12]]}},"alternative-id":["10.1128\/AAC.44.12.3389-3394.2000"],"URL":"https:\/\/doi.org\/10.1128\/aac.44.12.3389-3394.2000","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12]]},"assertion":[{"value":"2000-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-09-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}