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UE"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033\/FEDER, UE"]}]},{"name":"ULL-Fundaci\u00f3n Bancaria La Caixa-Fundaci\u00f3n Bancaria Cajacanarias 2024","award":["CC20230222"],"award-info":[{"award-number":["CC20230222"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Leishmaniasis and Chagas disease are parasitic diseases considered to be among the most important neglected diseases, with implications for both developed and developing countries. Currently, there are no effective therapeutic treatments for these diseases due to challenges in drug administration, high toxicity, high costs, and drug resistance. In this study, a series of eleven thymol derivatives were designed, synthesized, and evaluated for their in vitro kinetoplastid activity against Leishmania amazonensis and Trypanosoma cruzi, as well as their cytotoxicity against a murine macrophage cell line. The most active compounds, thymol anysoate (9) and thymol picolinate (10), displayed the highest kinetoplastid activity with IC50 values of 22.87 and 25.16 \u00b5M against L. amazonensis and T. cruzi, respectively. Notably, both compounds demonstrated an excellent selectivity index against the mammal cell line. Structure\u2013activity relationship studies revealed that the ester group plays a crucial role in activity. The most promising derivatives, 9 and 10, activate autophagy and apoptosis-like processes in the treated cells. Atomic force microscopy observations showed that derivative 9 induces the formation of cytoplasmic vacuoles, indicating an autophagic process, and drug-likeness analysis revealed that it meets all the pharmacokinetic criteria. Overall, these results highlight derivative 9 as a potential lead compound for the development of new drugs for the treatment of Trypanosomatidae infections and warrants further studies to elucidate the cell death cascade involved.<\/jats:p>","DOI":"10.3390\/antibiotics14040383","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T11:24:39Z","timestamp":1744025079000},"page":"383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanism Insight of Cell Death Signaling by Thymol Derivatives on Trypanosomatidae Protozoan Parasites"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6213-4835","authenticated-orcid":false,"given":"Amani","family":"Omrani","sequence":"first","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, 38296 La Laguna, Tenerife, Spain"},{"name":"Laboratory of Functional Physiology and Valorization of Bio-Ressources, Higher Institute of Biotechnology of Beja, University of Jendouba, Beja 382-9000, Tunisia"},{"name":"Instituto Universitario de Bio-Org\u00e1nica Antonio Gonz\u00e1lez, Departamento de Qu\u00edmica Org\u00e1nica, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez 2, 38206 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meriam","family":"Ben Youssef","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, 38296 La Laguna, Tenerife, Spain"},{"name":"Laboratory of Functional Physiology and Valorization of Bio-Ressources, Higher Institute of Biotechnology of Beja, University of Jendouba, Beja 382-9000, Tunisia"},{"name":"Instituto Universitario de Bio-Org\u00e1nica Antonio Gonz\u00e1lez, Departamento de Qu\u00edmica Org\u00e1nica, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez 2, 38206 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Sifaoui","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, 38296 La Laguna, Tenerife, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, C\/Sta. 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Bazzocchi","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Bio-Org\u00e1nica Antonio Gonz\u00e1lez, Departamento de Qu\u00edmica Org\u00e1nica, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez 2, 38206 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-1401","authenticated-orcid":false,"given":"Hichem","family":"Sebai","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Physiology and Valorization of Bio-Ressources, Higher Institute of Biotechnology of Beja, University of Jendouba, Beja 382-9000, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Lorenzo-Morales","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, 38296 La Laguna, Tenerife, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, C\/Sta. Mar\u00eda Soledad s\/n, 38200 La Laguna, Tenerife, Spain"},{"name":"Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red, \u00c1rea de Enfermedades Infecciosas, Instituto de Salud (CIBERINFEC) Carlos III, Av. 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