{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T03:52:22Z","timestamp":1773719542947,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Science Fund","award":["P 27814-B22"],"award-info":[{"award-number":["P 27814-B22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Leishmaniasis is a vector-borne disease caused by protozoal Leishmania parasites. Previous studies have shown that endoperoxides (EP) can selectively kill Leishmania in host cells. Therefore, we studied in this work a set of new anthracene-derived EP (AcEP) together with their non-endoperoxidic analogs in model systems of Leishmania tarentolae promastigotes (LtP) and J774 macrophages for their antileishmanial activity and selectivity. The mechanism of effective compounds was explored by studying their reaction with iron (II) in chemical systems and in Leishmania. The correlation of structural parameters with activity demonstrated that in this compound set, active compounds had a LogPOW larger than 3.5 and a polar surface area smaller than 100 \u00c52. The most effective compounds (IC50 in LtP &lt; 2 \u00b5M) with the highest selectivity (SI &gt; 30) were pyridyl-\/tert-butyl-substituted AcEP. Interestingly, also their analogs demonstrated activity and selectivity. In mechanistic studies, it was shown that EP were activated by iron in chemical systems and in LtP due to their EP group. However, the molecular structure beyond the EP group significantly contributed to their differential mitochondrial inhibition in Leishmania. The identified compound pairs are a good starting point for subsequent experiments in pathogenic Leishmania in vitro and in animal models.<\/jats:p>","DOI":"10.3390\/molecules27206846","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T22:21:11Z","timestamp":1665699671000},"page":"6846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antileishmanial Anthracene Endoperoxides: Efficacy In Vitro, Mechanisms and Structure-Activity Relationships"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-6789","authenticated-orcid":false,"given":"Laura","family":"Machin","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Institute of Pharmacology and Toxicology, University of Veterinary Medicine, 1210 Vienna, Austria"},{"name":"Pharmacy Department, Institute of Pharmacy and Food Sciences, University of Havana, Havana 13600, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Piontek","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Institute of Pharmacology and Toxicology, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Todhe","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Institute of Pharmacology and Toxicology, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Staniek","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Institute of Pharmacology and Toxicology, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-809X","authenticated-orcid":false,"given":"Lianet","family":"Monzote","sequence":"additional","affiliation":[{"name":"Parasitology Department, Institute of Tropical Medicine \u201cPedro Kouri\u201d, Havana 11400, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Fudickar","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, University of Potsdam, 14476 Potsdam, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3576-7426","authenticated-orcid":false,"given":"Torsten","family":"Linker","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, University of Potsdam, 14476 Potsdam, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-0201","authenticated-orcid":false,"given":"Lars","family":"Gille","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Institute of Pharmacology and Toxicology, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrmicro2608","article-title":"Leishmaniasis: Complexity at the host-pathogen interface","volume":"9","author":"Kaye","year":"2011","journal-title":"Nat. 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