Valorizing Constituents of Cashew Nut Shell Liquid toward the Sustainable Development of New Drugs against Chagas Disease

• Published in: ACS infectious diseases Vol. 9; no. 7; pp. 1334 - 1345
• Main Authors: Nunes Lemes, Laís Flávia, Magoulas, George E., Souza de Oliveira, Andressa, Barrias, Emile, de Camargo Nascente, Luciana, Granado, Renato, Teixeira de Macedo Silva, Sara, Assimomytis, Nikos, de Souza, Wanderley, Bolognesi, Maria Laura, Romeiro, Luiz Antonio Soares, Calogeropoulou, Theodora
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14-07-2023
• Subjects: Anacardium; Chagas Disease - drug therapy; Chagas Disease - parasitology; Lipids; Nuts; Sustainable Development; Trypanocidal Agents; antiparasitic activity; ether phospholipids; ultrastructural studies; cashew nut shell liquid; Trypanosoma cruzi
• ISSN: 2373-8227; 2373-8227
• DOI: 10.1021/acsinfecdis.3c00076

Six new ether phospholipid analogues encompassing constituents from cashew nut shell liquid as the lipid portion were synthesized in an effort to valorize byproducts of the cashew industry toward the generation of potent compounds against Chagas disease. Anacardic acids, cardanols, and cardols were used as the lipid portions and choline as the polar headgroup. The compounds were evaluated for their in vitro antiparasitic activity against different developmental stages of Trypanosoma cruzi. Compounds 16 and 17 were found to be the most potent against T. cruzi epimastigotes, trypomastigotes, and intracellular amastigotes exhibiting selectivity indices against the latter 32-fold and 7-fold higher than current drug benznidazole, respectively. Hence, four out of six analogues can be considered as hit-compounds toward the sustainable development of new treatments for Chagas disease, based on inexpensive agro-waste material.