{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:50:27Z","timestamp":1792619427033,"version":"4.5.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,11,12]]},"abstract":"<jats:p>\n                    A novel fungal metabolite, apicidin\n [cyclo(\n                    <jats:italic>N<\/jats:italic>\n                    -\n                    <jats:italic>O<\/jats:italic>\n                    -methyl-\n                    <jats:sc>l<\/jats:sc>\n                    -tryptophanyl-\n                    <jats:sc>l<\/jats:sc>\n                    -isoleucinyl-\n                    <jats:sc>d<\/jats:sc>\n                    -pipecolinyl-\n                    <jats:sc>l<\/jats:sc>\n                    -2-amino-8-oxodecanoyl)],\n that exhibits potent, broad spectrum antiprotozoal activity\n                    <jats:italic>in\n vitro<\/jats:italic>\n                    against Apicomplexan parasites has been identified. It is\n also orally and parenterally active\n                    <jats:italic>in vivo<\/jats:italic>\n                    against\n                    <jats:italic>Plasmodium berghei<\/jats:italic>\n                    malaria in mice. Many Apicomplexan\n parasites cause serious, life-threatening human and animal diseases,\n such as malaria, cryptosporidiosis, toxoplasmosis, and coccidiosis, and\n new therapeutic agents are urgently needed. Apicidin\u2019s antiparasitic\n activity appears to be due to low nanomolar inhibition of Apicomplexan\n histone deacetylase (HDA), which induces hyperacetylation of histones\n in treated parasites. The acetylation\u2013deacetylation of histones is a\n thought to play a central role in transcriptional control in eukaryotic\n cells. Other known HDA inhibitors were also evaluated and found to\n possess antiparasitic activity, suggesting that HDA is an attractive\n target for the development of novel antiparasitic agents.\n                  <\/jats:p>","DOI":"10.1073\/pnas.93.23.13143","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"13143-13147","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":497,"title":["Apicidin: A novel antiprotozoal agent that inhibits parasite\u2009histone\u2009deacetylase"],"prefix":"10.1073","volume":"93","author":[{"given":"Sandra\u2009J.","family":"Darkin-Rattray","sequence":"first","affiliation":[{"name":"Departments of Parasite Biochemistry and Cell Biology,\r Medicinal Chemistry, and Natural Products Drug\r Discovery, Merck Research Laboratories, P.O. 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