{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:07:00Z","timestamp":1788930420566,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR31714779"],"award-info":[{"award-number":["BR31714779"]}]},{"award":["BR31714779"],"award-info":[{"award-number":["BR31714779"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"University of Buenos Aires","doi-asserted-by":"publisher","award":["UBACYT 20020220300118BA"],"award-info":[{"award-number":["UBACYT 20020220300118BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"award":["UBACYT 20020220300118BA"],"award-info":[{"award-number":["UBACYT 20020220300118BA"]}],"id":[{"id":"https:\/\/ror.org\/0081fs513","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Agency for Science and Technology Promotion","award":["PICT 2020 SERIEA-03061"],"award-info":[{"award-number":["PICT 2020 SERIEA-03061"]}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"crossref","award":["PIP 11220250100209CO"],"award-info":[{"award-number":["PIP 11220250100209CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PIP 11220250100209CO"],"award-info":[{"award-number":["PIP 11220250100209CO"]}],"id":[{"id":"https:\/\/ror.org\/03cqe8w59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>This study presents a comparative in vitro evaluation of 24 natural sesquiterpene \u03b3-lactones and selected semisynthetic derivatives against three trypanosomatid parasites responsible for neglected tropical diseases: Trypanosoma brucei brucei, Trypanosoma cruzi, and Leishmania amazonensis. The compounds were screened for antiparasitic activity across different parasite life stages, and their cytotoxicity was assessed in mammalian cells. Several compounds demonstrated high inhibitory activity (&gt;95%) at 10 \u00b5g\/mL, including estafiatin (1), grossheimin (4), cynaropicrin (5), argolide (2) derivatives, and arglabin (23). However, a marked decrease in activity was observed at lower concentrations and in intracellular parasite models, particularly for T. cruzi and L. amazonensis amastigotes. Among the tested compounds, dihydroargolide (3) and pulchellin C (19) exhibited comparatively lower cytotoxicity and were further evaluated, yielding IC50 values of 10.51 \u00b1 1.72 \u00b5g\/mL and 2.51 \u00b1 1.13 \u00b5g\/mL against T. b. brucei, respectively. Against L. amazonensis promastigotes, estafiatin (1), 8\u03b1-chloroacetoxygrossheimin (12), and arglabin (23) showed IC50 values of 0.16 \u00b1 0.13, 0.35 \u00b1 0.18, and 0.58 \u00b1 0.11 \u00b5g\/mL, respectively, although their selectivity indices remained limited. Comparative analysis of the dataset indicates that specific structural elements, such as the \u03b1-methylene-\u03b3-lactone moiety and selected substituents (e.g., epoxy and acetyl groups), may influence antiparasitic activity in a species-dependent manner. At the same time, the generally low selectivity indices and reduced activity in intracellular models highlight important limitations of these compounds as direct drug leads. Overall, this work provides a systematic comparative dataset and identifies preliminary structure\u2013activity trends that may guide further chemical optimization of sesquiterpene \u03b3-lactones as antiparasitic hit compounds.<\/jats:p>","DOI":"10.3390\/ijms27177971","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:30:02Z","timestamp":1788798602000},"page":"7971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antiparasitic Activity of Sesquiterpene \u03b3-Lactones and the Search for New Pharmaceutical Agents"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7588-6174","authenticated-orcid":false,"given":"Sergazy M.","family":"Adekenov","sequence":"first","affiliation":[{"name":"JSC \u201cResearch Production Center \u201cPhytochemistry\u201d, 100009 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Laura C.","family":"Laurella","sequence":"additional","affiliation":[{"name":"CONICET-Universidad de Buenos Aires, Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), Buenos Aires C1113AAD, Argentina"},{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Farmacognosia, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6030-620X","authenticated-orcid":false,"given":"Shynggys","family":"Sergazy","sequence":"additional","affiliation":[{"name":"JSC \u201cResearch Production Center \u201cPhytochemistry\u201d, 100009 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5901-9166","authenticated-orcid":false,"given":"Rachel Napoles","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Farmacognosia, Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Augusto E.","family":"Bivona","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Inmunolog\u00eda, Buenos Aires C1113AAD, Argentina"},{"name":"CONICET-Universidad de Buenos Aires, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3592-3951","authenticated-orcid":false,"given":"Juan M.","family":"Viecenz","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Parasitolog\u00eda, ANLIS \u201cCarlos G. 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