{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:40:13Z","timestamp":1790509213001,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[1998,4,1]],"date-time":"1998-04-01T00:00:00Z","timestamp":891388800000},"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":[[1998,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cyclosporine and nonimmunosuppressive cyclosporin (CS) analogs were demonstrated to be potent inhibitors of the growth of the intracellular parasite\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    in short-term (48-h) in vitro cultures. Fifty-percent inhibitory concentrations (IC\n                    <jats:sub>50<\/jats:sub>\n                    s) were 0.4 \u03bcM for SDZ 033-243, 1.0 \u03bcM for SDZ PSC-833, and 1.5 \u03bcM for cyclosporine. Two other analogs were less effective than cyclosporine: the IC\n                    <jats:sub>50<\/jats:sub>\n                    of SDZ 205-549 was 5 \u03bcM, and that of SDZ 209-313 was 7 \u03bcM. These were much lower than the IC\n                    <jats:sub>50<\/jats:sub>\n                    of 85 \u03bcM of paromomycin, a standard positive control for in vitro drug assays for this parasite. In addition, intracellular growth of excysted sporozoites that had been incubated for 1 h in cyclosporine was significantly reduced, suggesting that the drug can inhibit sporozoite invasion. The cellular activities of the CS analogs used have been characterized for mammalian cells and protozoa. The two analogs that were most active in inhibiting\n                    <jats:italic>C. parvum<\/jats:italic>\n                    , SDZ PSC-833 and SDZ 033-243, bind weakly to cyclophilin, a peptidyl proline isomerase which is the primary target of cyclosporine and CS analogs. However, they are potent modifiers of the activity of the P glycoproteins\/multidrug resistance (MDR) transporters, members of the ATP-binding cassette (ABC) superfamily. Hence, both cyclophilin and some ABC transporters may be targets for this class of drugs, although drugs that preferentially interact with the latter are more potent. Cyclosporine (0.5 \u03bcM) had no significant chemosensitizing activity. That is, it did not significantly increase sensitivity to paromomycin, suggesting that an ABC transporter is not critical in the efflux of this drug. Cyclosporine at concentrations up to 50 \u03bcM was not toxic to host Caco-2 cells in the CellTiter 96 assay. The results of this study complement those of studies of the inhibitory effect of cyclosporine and CS analogs on other apicomplexan parasites,\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    ,\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    , and\n                    <jats:italic>Toxoplasma gondii.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1128\/aac.42.4.843","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T20:31:10Z","timestamp":1539030670000},"page":"843-848","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Cyclosporin Analogs Inhibit In Vitro Growth of\n                    <i>Cryptosporidium parvum<\/i>"],"prefix":"10.1128","volume":"42","author":[{"given":"Margaret E.","family":"Perkins","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Division of Environmental Health Sciences, Columbia University School of Public Health, New York, New York 10032,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa W.","family":"Wu","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Environmental Health Sciences, Columbia University School of Public Health, New York, New York 10032,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie M.","family":"Le Blancq","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Environmental Health Sciences, Columbia University School of Public Health, New York, New York 10032,1 and"},{"name":"<!--label omitted: 2-->Center for Environmental Research and Conservation, Columbia University, New York, New York 100272"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5381"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90279-8"},{"key":"e_1_3_2_4_2","unstructured":"Blagburn B. 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