Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships
Correspondence: mwalter@utalca.cl; Tel.: +56-71-2418866.
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| Format: | article |
| Language: | English |
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2026
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| Online Access: | https://doi.org/10.3390/ph19050801 http://hdl.handle.net/20.500.14066/4793 |
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| _version_ | 1870612066354593792 |
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| author | Pertino, Mariano Walter |
| author2 | Carreño González, Patricio Venegas González, Camila Schmeda Hirschmann, Guillermo Vega Gómez, María Celeste Rolón, Miriam Soledad Rojas de Arias, Gladys Antonieta |
| author2_role | author author author author author author |
| author_browse | Carreño González, Patricio Pertino, Mariano Walter Rojas de Arias, Gladys Antonieta Rolón, Miriam Soledad Schmeda Hirschmann, Guillermo Vega Gómez, María Celeste Venegas González, Camila |
| author_facet | Pertino, Mariano Walter Carreño González, Patricio Venegas González, Camila Schmeda Hirschmann, Guillermo Vega Gómez, María Celeste Rolón, Miriam Soledad Rojas de Arias, Gladys Antonieta |
| author_role | author |
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| bitstream.checksumAlgorithm.fl_str_mv | MD5 MD5 MD5 MD5 MD5 |
| bitstream.url.fl_str_mv | http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/1/Triazole-functionalized%20jatrophone%20derivatives%20as%20antiprotozoal%20agents%20against%20Trypanosoma%20cruzi%20%20synthesis%2c%20biological%20evaluation%20and%20structure-activity%20relationships.pdf http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/4/pharmaceuticals-4297843-supplementary.pdf http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/2/license_rdf http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/3/license.txt http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/5/Triazole-functionalized%20jatrophone%20derivatives%20as%20antiprotozoal%20agents%20against%20Trypanosoma%20cruzi%20%20synthesis.jpg |
| dc.creator.none.fl_str_mv | Pertino, Mariano Walter Carreño González, Patricio Venegas González, Camila Schmeda Hirschmann, Guillermo Vega Gómez, María Celeste Rolón, Miriam Soledad Rojas de Arias, Gladys Antonieta |
| dc.date.accessioned.none.fl_str_mv | 2026-06-25T18:24:44Z |
| dc.date.available.none.fl_str_mv | 2026-06-25T18:24:44Z |
| dc.date.issued.none.fl_str_mv | 2026-05-21 |
| dc.format.extent.es.fl_str_mv | 16 páginas |
| dc.identifier.citation.en.fl_str_mv | Pertino, M. W., Carreño Gonzalez, P., Venegas González, C., Schmeda-Hirschmann, G., Vega Gómez, C., Rolón, M., & Rojas de Arias, A. (2026). Triazole-Functionalized Jatrophone Derivatives as Antiprotozoal Agents Against Trypanosoma cruzi: Synthesis, Biological Evaluation and Structure—Activity Relationships. Pharmaceuticals, 19(5), 801. https://doi.org/10.3390/ph19050801 |
| dc.identifier.doi.es.fl_str_mv | 10.3390/ph19050801 |
| dc.identifier.essn.es.fl_str_mv | 1424-8247 |
| dc.identifier.other.es.fl_str_mv | https://doi.org/10.3390/ph19050801 |
| dc.identifier.uri.none.fl_str_mv | http://hdl.handle.net/20.500.14066/4793 |
| dc.language.iso.es.fl_str_mv | eng |
| dc.publisher.es.fl_str_mv | Multidisciplinary Digital Publishing Institute |
| dc.rights.*.fl_str_mv | Atribución/Reconocimiento 4.0 Internacional |
| dc.rights.accessRights.es.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.rights.uri.*.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.subject.other.es.fl_str_mv | Antiprotozoal activity Click chemistry Jatrophone Triazole hybrids Trypanosoma cruzi |
| dc.title.es.fl_str_mv | Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships |
| dc.type.es.fl_str_mv | info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | Correspondence: mwalter@utalca.cl; Tel.: +56-71-2418866. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | CONACYT_2f564d8baf7fa41e465299ec1b6a3831 |
| identifier_str_mv | Pertino, M. W., Carreño Gonzalez, P., Venegas González, C., Schmeda-Hirschmann, G., Vega Gómez, C., Rolón, M., & Rojas de Arias, A. (2026). Triazole-Functionalized Jatrophone Derivatives as Antiprotozoal Agents Against Trypanosoma cruzi: Synthesis, Biological Evaluation and Structure—Activity Relationships. Pharmaceuticals, 19(5), 801. https://doi.org/10.3390/ph19050801 10.3390/ph19050801 1424-8247 |
| language | eng |
| network_acronym_str | CONACYT |
| network_name_str | Repositorio Institucional CONACYT |
| oai_identifier_str | oai:repositorio.conacyt.gov.py:20.500.14066/4793 |
| publishDate | 2026 |
| publishDateSort | 2026 |
| repository.mail.fl_str_mv | repositorio.institucional@conacyt.gov.py |
| repository.name.fl_str_mv | Repositorio Institucional CONACYT |
| repository_id_str | |
| rights_invalid_str_mv | Atribución/Reconocimiento 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ |
| spelling | e80ec11b-1c10-42ca-b589-ffcf1a4d8463600db086c3d-a7c3-4796-946c-237a726d245b600f613bd67-274a-40c2-ac52-f0dfba9bac9b6002c2eb3f4-15b5-44ec-9df1-c17ca59be99360011456000000-0001-6291-431610066009976000000-0002-6207-18702026-06-25T18:24:44Z2026-06-25T18:24:44Z2026-05-21Pertino, M. W., Carreño Gonzalez, P., Venegas González, C., Schmeda-Hirschmann, G., Vega Gómez, C., Rolón, M., & Rojas de Arias, A. (2026). Triazole-Functionalized Jatrophone Derivatives as Antiprotozoal Agents Against Trypanosoma cruzi: Synthesis, Biological Evaluation and Structure—Activity Relationships. Pharmaceuticals, 19(5), 801. https://doi.org/10.3390/ph19050801https://doi.org/10.3390/ph19050801http://hdl.handle.net/20.500.14066/479310.3390/ph190508011424-8247Correspondence: mwalter@utalca.cl; Tel.: +56-71-2418866.This article belongs to the Section Medicinal Chemistry.Background/Objectives: Jatrophone is a bioactive diterpenoid with reported antitrypanosomal activity; however, its development as a lead compound is limited by pronounced cytotoxicity toward mammalian cells. This study aimed to explore the structural modification of jatrophone through triazole functionalization to modulate its antiparasitic activity and improve selectivity against Trypanosoma cruzi. Methods: A series of mono- and bis-triazole jatrophone derivatives was semi-synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) from a stereoselectively prepared diazido intermediate. Jatrophone, its azido precursor, and the synthesized triazole derivatives were evaluated in vitro against T. cruzi epimastigotes and intracellular amastigotes. Cytotoxicity toward mammalian host cells was assessed in parallel to determine selectivity indices. Results: Jatrophone exhibited potent activity against epimastigotes but showed poor selectivity due to significant mammalian cell toxicity. Introduction of azide and triazole functionalities altered the biological profile of the parent scaffold, leading to derivatives with reduced cytotoxicity and improved selectivity in extracellular assays. Among the evaluated compounds, a mono-triazole derivative bearing a methylene-linked cycloalkyl substituent retained antiparasitic activity while displaying markedly lower toxicity toward mammalian cells. However, in the intracellular amastigote model, most derivatives demonstrated a substantial reduction in selectivity, indicating limited translation of extracellular activity to the intracellular parasite stage. Conclusions: Triazole functionalization of the jatrophone scaffold represents a viable strategy to modulate its biological properties and reduce host-cell toxicity. Nevertheless, the reduced efficacy observed in intracellular assays underscores the limitations of epimastigote-based screening and highlights the challenges in developing selective intracellular antitrypanosomal agents from the jatrophone scaffold.Consejo Nacional de Ciencia y TecnologíaPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Sistema Nacional de Investigadores16 páginasengMultidisciplinary Digital Publishing InstituteAtribución/Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccess© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.Antiprotozoal activityClick chemistryJatrophoneTriazole hybridsTrypanosoma cruziTriazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationshipsinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion5Pharmaceuticals19Pertino, Mariano WalterCarreño González, PatricioVenegas González, CamilaSchmeda Hirschmann, GuillermoVega Gómez, María CelesteRolón, Miriam SoledadRojas de Arias, Gladys AntonietaORIGINALTriazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi synthesis, biological evaluation and structure-activity relationships.pdfTriazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi synthesis, biological evaluation and structure-activity relationships.pdfArtículo científicoapplication/pdf2710401http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/1/Triazole-functionalized%20jatrophone%20derivatives%20as%20antiprotozoal%20agents%20against%20Trypanosoma%20cruzi%20%20synthesis%2c%20biological%20evaluation%20and%20structure-activity%20relationships.pdf6eb23800d68b58c0972738e60774d070MD51pharmaceuticals-4297843-supplementary.pdfpharmaceuticals-4297843-supplementary.pdfInformación complementariaapplication/pdf8076834http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/4/pharmaceuticals-4297843-supplementary.pdf3e86efab73abc305b702c20bf3229575MD54CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8908http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/2/license_rdf0175ea4a2d4caec4bbcc37e300941108MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81698http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/3/license.txt858b22fda432bd774e469302988c1974MD53THUMBNAILTriazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi synthesis.jpgTriazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi synthesis.jpgArtículo científicoimage/jpeg508130http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4793/5/Triazole-functionalized%20jatrophone%20derivatives%20as%20antiprotozoal%20agents%20against%20Trypanosoma%20cruzi%20%20synthesis.jpgdcd4dc51d4d3d8bcdbf4e262945f444aMD5520.500.14066/4793oai:repositorio.conacyt.gov.py:20.500.14066/47932026-06-25 19:04:23.826Repositorio Institucional CONACYTrepositorio.institucional@conacyt.gov.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 |
| spellingShingle | Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships Pertino, Mariano Walter Antiprotozoal activity Click chemistry Jatrophone Triazole hybrids Trypanosoma cruzi |
| status_str | publishedVersion |
| title | Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships |
| title_full | Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships |
| title_fullStr | Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships |
| title_full_unstemmed | Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships |
| title_short | Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships |
| title_sort | Triazole-functionalized jatrophone derivatives as antiprotozoal agents against Trypanosoma cruzi : synthesis, biological evaluation and structure—activity relationships |
| topic | Antiprotozoal activity Click chemistry Jatrophone Triazole hybrids Trypanosoma cruzi |
| url | https://doi.org/10.3390/ph19050801 http://hdl.handle.net/20.500.14066/4793 |