{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:31:33Z","timestamp":1779100293906,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>The apicomplexan parasite, <jats:italic>Theileria annulata<\/jats:italic>, is the most prevalent hemoprotozoan in livestock, causing significant economic losses worldwide. It is essential to develop new and improved therapeutics, as current control measures are compromised by the development of resistance against the only available antitheilerial drug, buparvaquone (BPQ). Histone deacetylase inhibitors (HDACi) were shown to treat cancer effectively and revealed <jats:italic>in vitro<\/jats:italic> antiparasitic activity against apicomplexan parasites such as <jats:italic>Plasmodium<\/jats:italic> and <jats:italic>Toxoplasma<\/jats:italic>. In this study, we investigated the antitheilerial activity of the four anti-cancer HDACi (vorinostat, romidepsin, belinostat, and panobinostat) against the schizont stage of <jats:italic>T. annulata<\/jats:italic> parasites. All four HDACi showed potent activity and increased hyperacetylation of the histone-4 protein. However, based on the low host cell cytotoxicity and IC<jats:sub>50<\/jats:sub> values, vorinostat (0.103 \u03bcM) and belinostat (0.069 \u03bcM) were the most effective showing antiparasitic activity. The parasite-specific activities of the HDACi (vorinostat and belinostat) were evaluated by western blotting using parasite-specific antibodies and <jats:italic>in silico<\/jats:italic> analysis. Both vorinostat and belinostat reduced the <jats:italic>Theileria<\/jats:italic> infected cell viability by downregulating anti-apoptotic proteins and mitochondrial dysfunction, leading to caspase-dependent cell apoptosis. The HDACi caused irreversible and antiproliferative effects on the <jats:italic>Theileria<\/jats:italic> infected cell lines. Our results collectively showed that vorinostat and belinostat could be used as an alternative therapy for treating <jats:italic>Theileria<\/jats:italic> parasites.<\/jats:p>","DOI":"10.3389\/fmicb.2021.759817","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T08:28:58Z","timestamp":1637310538000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors"],"prefix":"10.3389","volume":"12","author":[{"given":"Madhumanti","family":"Barman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonam","family":"Kamble","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonti","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasundhra","family":"Bhandari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siva","family":"Singothu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debabrata","family":"Dandasena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akash","family":"Suresh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paresh","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1128\/AAC.00729-08","article-title":"Novel inhibitor of plasmodium histone deacetylase that cures p. berghei- infected mice.","volume":"53","author":"Agbor-Enoh","year":"2009","journal-title":"Antimicrob. 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