Trypanocidal and toxicological assessment in vitro and in silico of three sesquiterpene lactones from Asteraceae plant species

We report the effect of the Sesquiterpene Lactones Ambrosin, Incomptine B and Glaucolide E against seven strains of Trypanosoma 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 μM, respectively). These compounds were more potent than the drugs Benznidazole (IC50 > 400 μM) and Nifurtimox (IC50 = 199.7 to >400 μM). 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 G/H 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.