{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:18:57Z","timestamp":1784956737213,"version":"3.55.0"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01 AI15477"],"award-info":[{"award-number":["R01 AI15477"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,4,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              In an effort to identify novel compounds with potent inhibition against\n              <jats:italic>Toxoplasma gondii,<\/jats:italic>\n              a phenotypic screen was performed utilizing a library of 683 pure compounds derived primarily from terrestrial and marine fungi. An initial screen with a fixed concentration of 5 \u00b5M yielded 91 hits with inhibition comparable to an equal concentration of artemisinin. These compounds were then triaged based on known biological and chemical concerns and liabilities. From these, 49 prioritized compounds were tested in a dose response format with\n              <jats:italic>T. gondii<\/jats:italic>\n              and human foreskin fibroblasts (HFFs) for cytotoxicity. Ten compounds were identified with an IC\n              <jats:sub>50<\/jats:sub>\n              less than 150 nM and a selectivity index (SI) greater than 100. An additional eight compounds demonstrated submicromolar IC\n              <jats:sub>50<\/jats:sub>\n              and SI values equal to or greater than 35. While the majority of these scaffolds have been previously implicated against apicomplexan parasites, their activities in\n              <jats:italic>T. gondii<\/jats:italic>\n              were largely unknown. Herein, we report the\n              <jats:italic>T. gondii<\/jats:italic>\n              activity of these compounds with chemotypes including xanthoquinodins, peptaibols, heptelidic acid analogs, and fumagillin analogs, with multiple compounds demonstrating exceptional potency in\n              <jats:italic>T. gondii<\/jats:italic>\n              and limited toxicity to HFFs at the highest concentrations tested.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Current therapeutics for treating toxoplasmosis remain insufficient, demonstrating high cytotoxicity, poor bioavailability, limited efficacy, and drug resistance. Additional research is needed to develop novel compounds with high efficacy and low cytotoxicity. The success of artemisinin and other natural products in treating malaria highlights the potential of natural products as anti-protozoan therapeutics. However, the exploration of natural products in\n              <jats:italic>T. gondii<\/jats:italic>\n              drug discovery has been less comprehensive, leaving untapped potential. By leveraging the resources available for the malaria drug discovery campaign, we conducted a phenotypic screen utilizing a set of natural products previously screened against\n              <jats:italic>Plasmodium falciparum<\/jats:italic>\n              . Our study revealed 18 compounds with high potency and low cytotoxicity in\n              <jats:italic>T. gondii<\/jats:italic>\n              , including four novel scaffolds with no previously reported activity in\n              <jats:italic>T. gondii<\/jats:italic>\n              . These new scaffolds may serve as starting points for the development of toxoplasmosis therapeutics but could also serve as tool compounds for target identification studies using chemogenomic approach.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.04142-23","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T14:00:44Z","timestamp":1709215244000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Identification of fungal natural products with potent inhibition in\n            <i>Toxoplasma gondii<\/i>"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4875-3613","authenticated-orcid":false,"given":"Tiantian","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla P.","family":"Godinez-Macias","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Collins","sequence":"additional","affiliation":[{"name":"Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u2019s University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Wendt","sequence":"additional","affiliation":[{"name":"Natural Products Discovery Group, Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krypton","family":"Carolino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debopam","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Cichewicz","sequence":"additional","affiliation":[{"name":"Natural Products Discovery Group, Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-2113","authenticated-orcid":false,"given":"Elizabeth A.","family":"Winzeler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fawpar.2019.e00054"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111711"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25071574"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01114-14"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00113"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.0c01370"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202200341"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.1c00341"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2009.01.006"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0953756299001859"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.3c00283"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.23.13143"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00462-10"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082826"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22122026"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112740"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.51.153"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02256576"},{"key":"e_1_3_2_23_2","first-page":"1989","article-title":"A phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancer","volume":"5","author":"Bhargava P","year":"1999","unstructured":"Bhargava P, Marshall JL, Rizvi N, Dahut W, Yoe J, Figuera M, Phipps K, Ong VS, Kato A, Hawkins MJ. 1999. A phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancer. Clin Cancer Res 5:1989\u20131995.","journal-title":"Clin Cancer Res"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12457"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.04142-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.04142-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T15:07:03Z","timestamp":1712070423000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.04142-23"}},"subtitle":[],"editor":[{"given":"Jian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,2]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,2]]}},"alternative-id":["10.1128\/spectrum.04142-23"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.04142-23","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,2]]},"assertion":[{"value":"2023-12-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e04142-23"}}