{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:40:14Z","timestamp":1790509214162,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI138774"],"award-info":[{"award-number":["R21 AI138774"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["RC2AT005917"],"award-info":[{"award-number":["RC2AT005917"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Harbor Branch Oceanographic Institute Foundation","award":["Research Excellence and Discretionary Award"],"award-info":[{"award-number":["Research Excellence and Discretionary Award"]}]},{"name":"Poncin Fellowship Fund","award":["No Number"],"award-info":[{"award-number":["No Number"]}]},{"name":"Seattle Chapter of ARCS","award":["No Number"],"award-info":[{"award-number":["No Number"]}]},{"DOI":"10.13039\/100001906","name":"Washington Research Foundation","doi-asserted-by":"publisher","award":["No Number"],"award-info":[{"award-number":["No Number"]}],"id":[{"id":"10.13039\/100001906","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Cryptosporidium sp. are apicomplexan parasites that cause significant morbidity and possible mortality in humans and valuable livestock. There are no drugs on the market that are effective in the population most severely affected by this parasite. This study is the first high-throughput screen for potent anti-Cryptosporidium natural products sourced from a unique marine compound library. The Harbor Branch Oceanographic Institute at Florida Atlantic University has a collection of diverse marine organisms some of which have been subjected to medium pressure liquid chromatography to create an enriched fraction library. Numerous active compounds have been discovered from this library, but it has not been tested against Cryptosporidium parvum. A high-throughput in vitro growth inhibition assay was used to test 3764 fractions in the library, leading to the identification of 23 fractions that potently inhibited the growth of Cryptosporidium parvum. Bioassay guided fractionation of active fractions from a deep-sea sponge, Leiodermatium sp., resulted in the purification of leiodolide A, the major active compound in the organism. Leiodolide A displayed specific anti-Cryptosporidium activity at a half maximal effective concentration of 103.5 nM with selectivity indexes (SI) of 45.1, 11.9, 19.6 and 14.3 for human ileocecal colorectal adenocarcinoma cells (HCT-8), human hepatocellular carcinoma cells (Hep G2), human neuroblastoma cells (SH-SY5Y) and green monkey kidney cells (Vero), respectively. The unique structure of leiodolide A provides a valuable drug scaffold on which to develop new anti-Cryptosporidium compounds and supports the importance of screening natural product libraries for new chemical scaffolds.<\/jats:p>","DOI":"10.3390\/md20040240","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:28:39Z","timestamp":1648675719000},"page":"240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["High-Throughput Screening of a Marine Compound Library Identifies Anti-Cryptosporidium Activity of Leiodolide A"],"prefix":"10.3390","volume":"20","author":[{"given":"Rachel M.","family":"Bone Relat","sequence":"first","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, 100 Dairy Rd, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla L.","family":"Winder","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Bowden","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, 100 Dairy Rd, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0847-625X","authenticated-orcid":false,"given":"Esther A.","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara A.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley A.","family":"Pomponi","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill C.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4872-9776","authenticated-orcid":false,"given":"Amy E.","family":"Wright","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta M.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, 100 Dairy Rd, Pullman, WA 99164, USA"},{"name":"Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1971 Commonwealth Ave, St Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.watres.2016.09.013","article-title":"It\u2019s official\u2013Cryptosporidium is a gregarine: What are the implications for the water industry?","volume":"105","author":"Ryan","year":"2016","journal-title":"Water Res."},{"key":"ref_2","first-page":"1","article-title":"Surveillance for waterborne disease outbreaks and other health events associated with recreational water\u2014United States, 2007\u20132008","volume":"60","author":"Hlavsa","year":"2011","journal-title":"MMWR Surveill. 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