{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:25:51Z","timestamp":1776183951900,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Apicomplexan parasites, such as Toxoplasma gondii, Plasmodium spp., Babesia spp., and Cryptosporidium spp., cause significant morbidity and mortality. Existing treatments are problematic due to toxicity and the emergence of drug-resistant parasites. Because protozoan tubulin can be selectively disrupted by small molecules to inhibit parasite growth, we assembled an in vitro testing cascade to fully delineate effects of candidate tubulin-targeting drugs on Toxoplasma gondii and vertebrate host cells. Using this analysis, we evaluated clemastine, an antihistamine that has been previously shown to inhibit Plasmodium growth by competitively binding to the CCT\/TRiC tubulin chaperone as a proof-of-concept. We concurrently analyzed astemizole, a distinct antihistamine that blocks heme detoxification in Plasmodium. Both drugs have EC50 values of ~2 \u00b5M and do not demonstrate cytotoxicity or vertebrate microtubule disruption at this concentration. Parasite subpellicular microtubules are shortened by treatment with either clemastine or astemizole but not after treatment with pyrimethamine, indicating that this effect is not a general response to antiparasitic drugs. Immunoblot quantification indicates that the total \u03b1-tubulin concentration of 0.02 pg\/tachyzoite does not change with clemastine treatment. In conclusion, the testing cascade allows profiling of small-molecule effects on both parasite and vertebrate cell viability and microtubule integrity.<\/jats:p>","DOI":"10.3390\/ijms23010068","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:24:52Z","timestamp":1640168692000},"page":"68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Systematic Analysis of Clemastine, a Candidate Apicomplexan Parasite-Selective Tubulin-Targeting Agent"],"prefix":"10.3390","volume":"23","author":[{"given":"Izra","family":"Abbaali","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny A.","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shania D.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Haro-Ramirez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8810-3543","authenticated-orcid":false,"given":"Naomi S.","family":"Morrissette","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/EC.00225-14","article-title":"Targeting Toxoplasma tubules: Tubulin, microtubules, and associated proteins in a human pathogen","volume":"14","author":"Morrissette","year":"2015","journal-title":"Eukaryot. 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