{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:52:23Z","timestamp":1786121543082,"version":"build-2736575974"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Chagas disease (CD), caused by\n                      <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                      , remains a major public health challenge in Latin America, affecting more than 7 million people worldwide and approximately 100 million individuals at risk of infection. Current chemotherapy relies exclusively on benznidazole and nifurtimox, which present significant limitations, such as prolonged treatment regimens, severe side effects, and limited efficacy during the chronic phase of the disease. These drawbacks highlight the urgent need for novel therapeutic alternatives. In this context, natural products, particularly diterpenes, have attracted considerable attention due to their broad spectrum of biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Cafestol (\n                      <jats:bold>CF<\/jats:bold>\n                      ) and kahweol (\n                      <jats:bold>KW<\/jats:bold>\n                      ),\n                      <jats:italic>ent<\/jats:italic>\n                      -kaurane diterpenes found in\n                      <jats:italic>Coffea arabica<\/jats:italic>\n                      L., are recognized for their cardioprotective effects; however, their potential cardioprotective properties remain unexplored in the context of neglected diseases. This study aimed to evaluate the potential of\n                      <jats:bold>CF<\/jats:bold>\n                      and\n                      <jats:bold>KW<\/jats:bold>\n                      as trypanocidal agents and modulators of parasite-induced cardiac damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To investigate the trypanocidal potential of\n                      <jats:bold>CF<\/jats:bold>\n                      and\n                      <jats:bold>KW<\/jats:bold>\n                      , both compounds were tested individually and in combination (1:1) against two\n                      <jats:italic>T. cruzi<\/jats:italic>\n                      strains representing distinct discrete typing units (DTUs), Y and Tulahuen. Their activity was evaluated against bloodstream trypomastigotes, the infective stage, and intracellular amastigotes, the replicative stage in the mammalian host. An in vitro infection model using cardiac cells as host cells was also employed, allowing the investigation of the ability of these diterpenes to mitigate parasite-induced cellular damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results demonstrated that the combination of\n                      <jats:bold>CF<\/jats:bold>\n                      and\n                      <jats:bold>KW<\/jats:bold>\n                      enhanced trypanocidal activity against both\n                      <jats:italic>T. cruzi<\/jats:italic>\n                      strains tested. The\n                      <jats:bold>CF<\/jats:bold>\n                      +\n                      <jats:bold>KW<\/jats:bold>\n                      mixture showed significantly greater activity than the individual compounds against intracellular amastigotes of the Tulahuen strain (IC\u2085\u2080 = 9.6 \u00b5g\/mL) and bloodstream trypomastigotes of the Y strain (IC\u2085\u2080 = 10.4 \u00b5g\/mL). Against intracellular amastigotes of the Y strain, the combination remained active after 48 h of treatment (IC\u2085\u2080 = 13.3 \u00b5g\/mL).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Moreover, the\n                      <jats:bold>CF<\/jats:bold>\n                      and\n                      <jats:bold>KW<\/jats:bold>\n                      combination demonstrated superior efficacy in preserving sarcomere integrity in infected cardiac cells compared with the individual compounds. Based on these findings and considering their pharmacological potential,\n                      <jats:bold>CF<\/jats:bold>\n                      and\n                      <jats:bold>KW<\/jats:bold>\n                      represent promising candidates for the development of new therapeutic strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1885889","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:28:05Z","timestamp":1786080485000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cafestol and kahweol: coffee diterpenes with trypanocidal activity and cardioprotective effects"],"prefix":"10.3389","volume":"16","author":[{"given":"Juliana Magalh\u00e3es Chaves","family":"Barbosa","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Rio de Janeiro, RJ, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Macedo","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestrutura Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Rio de Janeiro, RJ, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio Junior Moreira","family":"Novaes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Anal\u00edtica - LAQUA, Departamento de Qu\u00edmica, Universidade Federal de Vi\u00e7osa","place":["Vi\u00e7osa, MG, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alice Esteves","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de An\u00e1lise de Aromas, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro, RJ, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Bernardino","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Rio de Janeiro, RJ, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Radler de","family":"Aquino Neto","sequence":"additional","affiliation":[{"name":"LADETEC, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro RJ, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Moraes","family":"de Rezende","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de An\u00e1lise de Aromas, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro, RJ, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Salom\u00e3o","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Rio de Janeiro, RJ, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana Galv\u00e3o","family":"de Melo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestrutura Celular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Rio de Janeiro, RJ, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/B978-0-12-385895-5.00003-7","article-title":"Gap junctions and chagas disease","volume":"76","author":"Adesse","year":"2011","journal-title":"Adv. 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