![\"\"](\"http:\/\/sites.unica.it\/pe2026\/files\/2026\/05\/Sousa-Janela-Joao.png\")
<\/figure>OC4 – Jo\u00e3o Sousa Janela<\/strong><\/p>\n\n\n\n CERES, Universidade de Coimbra, Faculdade de Farm\u00e1cia, Laborat\u00f3rio de Qu\u00edmica Farmac\u00eautica, Azinhaga de Santa Comba, P\u00f3lo III – P\u00f3lo das Ci\u00eancias da Sa\u00fade, 3000-548 Coimbra, Portugal<\/p>\n\n\n\n e-mail<\/a> –<\/strong> ORCID<\/a><\/strong><\/p>\n<\/div><\/div>\n\n\n\n <\/p>\n","protected":false},"excerpt":{"rendered":" OC4 – Jo\u00e3o Sousa Janela CERES, Universidade de Coimbra, Faculdade de Farm\u00e1cia, Laborat\u00f3rio de Qu\u00edmica Farmac\u00eautica, Azinhaga de Santa Comba, P\u00f3lo III – P\u00f3lo das Ci\u00eancias da Sa\u00fade, 3000-548 Coimbra, Portugal e-mail – ORCID New O-Prenylated […]<\/p>\n","protected":false},"author":9643,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1753","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1753","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/9643"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=1753"}],"version-history":[{"count":4,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1753\/revisions"}],"predecessor-version":[{"id":1786,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1753\/revisions\/1786"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=1753"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=1753"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=1753"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}New O-Prenylated Caffeic Acid Amides with Selective Toxicity Against Trypanosoma cruzi Amastigotes. Design, Synthesis and Structure-Activity Relationships<\/strong><\/td><\/tr> Jo\u00e3o Sousa Janela1<\/sup>, Lucas de Oliveira Pires2<\/sup>, Afonso Santine M. M. Velez2<\/sup>, F\u00e1bio da Costa Rocha2<\/sup>, D\u00e9bora Decot\u00e9-Ricardo3<\/sup>, Marco Edilson Freire de Lima2<\/sup>, Rosane Nora Castro2<\/sup>, Fernanda M. F. Roleira1<\/sup>, Elisi\u00e1rio J. Tavares da Silva1<\/sup><\/em>
1<\/sup><\/em> CERES, Universidade de Coimbra, Faculdade de Farm\u00e1cia, Laborat\u00f3rio de Qu\u00edmica Farmac\u00eautica, Azinhaga de Santa Comba, P\u00f3lo III – P\u00f3lo das Ci\u00eancias da Sa\u00fade, 3000-548 Coimbra, Portugal;
2<\/sup><\/em> Universidade Federal Rural do Rio de Janeiro, Instituto de Qu\u00edmica, Departamento de Qu\u00edmica Org\u00e2nica, BR 465, Km 07, CEP: 23.890-000, Serop\u00e9dica, RJ, Brasil;
3<\/sup><\/em> Universidade Federal Rural do Rio de Janeiro, Instituto de Veterin\u00e1ria, Departamento de Microbiologia e Imunologia Veterin\u00e1ria, BR 465, Km 07, CEP: 23.890-000, Serop\u00e9dica, RJ, Brasil;<\/td><\/tr>Abstract<\/strong>
Chagas\u2019 disease arises as an emergent parasitosis caused by the infection with Trypanosoma cruzi<\/em>, with only two drugs available for its treatment [1]. Cinnamic acid derivatives, such as esters and amides, are naturally occurring compounds from plant\u2019s metabolism. Their phenylpropanoid scaffold is privileged due to its structural simplicity and broad-spectrum biological properties, such as antiproliferative, antimicrobial, anti-inflammatory, antiparasitic, and antioxidant. In this context, they can be considered promising compounds in search for new drugs for Chagas\u2019 disease. Among them, caffeic acid and their esters and amides are often highlighted as the most attractive due to its assorted biological profile [2]. O<\/em>-prenylation is described as a structural modification that benefits the crossing of cell membranes [3], which seems appropriate when designing compounds to target single-celled protozoa. Based on this, it was designed and synthesized caffeic acid amides and their respective new 4-O<\/em>-prenylated analogues and tested their activity on amastigotes of T. cruzi<\/em>, and their selectivity using host cells. N<\/em>-alkylamides were more active against amastigotes in comparison to aromatic amides and displayed no toxicity against host cells. The most active compound (4-O<\/em>-prenyl-N<\/em>-pentylcaffeic acid amide) presented an IC50<\/sub> of 7.54 \u00b1 1.71 \u00b5M highlighting the importance of O<\/em>-prenylation on the catechol moiety for both toxicity and selectivity against T. cruzi<\/em>.<\/td><\/tr>References <\/strong>
[1] Jackson, Y. et al. Tolerance to nifurtimox and benznidazole in adult patients with chronic Chagas’ disease. J Antimicrob Chemother<\/em> 2020<\/strong>, 75<\/em>, 690-696. doi:10.1093\/jac\/dkz473
[2] Birkov\u00e1, A. et al. Caffeic acid: a brief overview of its presence, metabolism, and bioactivity. Bioact Compd health dis<\/em> 2020<\/strong>, 3(4)<\/em>, 74-81. doi:10.31989\/bchd.v3i4.692
[3] Oufensou, S. et al. Prenylated trans<\/em>-cinnamic esters and ethers against clinical Fusarium<\/em> spp.: repositioning of natural compounds in antimicrobial discovery. Molecules<\/em> 2021<\/strong>, 26<\/em>, 658. doi:10.3390\/molecules26030658
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Acknowledgments:<\/strong> The authors wish to acknowledge FCT \u2013 Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia for their financial support, including research unit funding (projects UID\/00102\/2025 and UID\/PRR\/00102\/2025) and PhD grant funding (reference 2022.13608.BD).<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n