And nifurtimox, each associated with extreme negative effects and debatable efficacy within the chronic phase, which highlights the want to seek out novel anti-trypanosomal therapies [4,6,7]. Recent efforts involve improvement of current therapies, like combining benznidazole with other compounds or dosing adjustments, molecular targeted drug development, repositioning of identified drugs, and discovery of novel compounds, like metal rug complexes, chemically modified nitro-aromatic molecules, or plant-derived solutions [7,27]. On the other hand, regardless of the a lot of promising documented drugs, other folks are necessary due to the slow and rigorous validation course of action and high downstream failure of drug candidates [7,16]. For instance, ravuconazole (E1224) and posaconazole were promising new drugs to treat chronic CD that had been unsuccessful in human trials as a result of absence of prolonged effects [28,29]. Plants represent an immense supply of potentially bioactive molecules with antiinfectious activity including against T. cruzi, as for instance rosemary (Rosmarinus officinalis L.) or green tea (Camellia sinensis (L.) Kuntze) [7], to name several. Pretty lately, some Amaryllidaceae alkaloids have been shown to inhibit T. cruzi growth, specifically hippeastrine, which was selective and specific against T. cruzi amastigotes (IC50 = 3.31 ) [30]. Even so, halophytes happen to be overlooked as prospective sources of anti-protozoal compounds, in particular against T. cruzi. For the most effective of our knowledge, only Oliveira et al. [12] screened various halophytes for in vitro anti-trypanosomal activity, obtaining a single extract from Juncus acutus L. roots able to lower T. cruzi’s development, though L ez et al. [11] located that -amyrine and quercetin isolated in the mangrove plant Pelliciera rhizophorae Planch. Triana have been active against T. cruzi. No reports were located in literature concerning the potential anti-parasitic activity of sea fennel and everlasting towards T. cruzi, although aerial components, including flowers, have reported anti-infective medicinal uses [14,15]. Within this context, this work evaluated for the first time the in vitro anti-trypanosomal activity of decoctions, tinctures, and critical oils (following the usage provided in folk practices) from these aromatic halophytes against intracellular amastigotes of two T. cruzi strains. Most of the tested samples did not yield promising anti-chagasic activity, either by low efficacy or as a result of higher host cell toxicity, specifically when in comparison with reference compound benznidazole (200 final concentration; Table 1). The exception was the decoction from sea fennel’s flowers that displayed moderate activity with 65 infection reduction without the need of substantially -Bicuculline methobromide Autophagy affecting the host cell. On the other hand, these results were obtained for the Y strain only, likely as a result of Sylvio X10/1 strain’s higher infectivity and superior number of intracellular amastigotes. Regardless of presenting higher genetic similarity, T. cruzi strains yield distinct susceptibility to distinct compounds, based on the target [31]. As an example, the activity of ergosterol biosynthesis inhibitors (posaconazole, ravuconazole, and other individuals) varied drastically depending on the T. cruzi strain assayed in vitro, below the AICAR custom synthesis identical assay situations [16]. Even for reference antichagasic compounds, which include benznidazole and nifurtimox, the in vitro activity is anticipated to vary amongst Y and Sylvio strains, which might be influenced by distinct infectivity profile-cellular invasion and differentiation capacities.