Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 125, Issue -, Pages 55-61Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2018.12.023
Keywords
Sesquiterpene lactones; Trypanosoma cruzi; Toxicology; Ambrosin; Incomptine B; Glaucolide E
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Funding
- NUATEI research program of the Instituto de Investigaciones Biomedicas-UNAM
- [IN210016 PAPIIT-UNAM]
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We report the effect of the Sesquiterpene Lactones Ambrosin, Incomptine B and Glaucolide E against seven strains of Ttypanosoma cruzi, the etiological agent of Chagas Disease. These compounds were isolated from Parthenium hysterophorus, Decachaeta incompta, and Vernonia liatroides, respectively. We evaluated by flow cytometry the viability of epimastigotes. Ambrosin was the most effective, then Incomptine B, and Glaucolide E (IC50 = 67.1, 123.7, and 215.1 mu M, respectively). These compounds were more potent than the drugs Benznidazole (IC50 > 400 mu M) and Nifurtimox (IC50 = 199.7 to > 400 mu M). Toxicity to mammalian Vero and Jurkat cells was also determined in vitro. All the compounds had a poor selective index (0.003-1.859). Toxicoinformatics is useful to forecast in silico toxicological and pharmacokinetic properties. Ambrosin and Incomptine B may not possess mutagenic, tumorigenic, or reproductive effects. Glaucolide E could possess a low mutagenic and high tumorigenic effects, and probably target the Amine Oxidase A, Prostaglandin and GIN Synthase I. Interestingly, Ambrosin, Incomptine B and Glaucolide E, comply with Lipinsky Rule of Five, indicating a suitable pharmacokinetic profile. Ambrosin and Incomptine B possess high trypanocidal activity, and pharmaceutical properties suitable for development; however, their safety profile should be optimized by structural modifications.
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