Apoptosis-like cell death upon kinetoplastid induction by compounds isolated from the brown algae Dictyota spiralis

Abstract

Background The in vitro activity of the brown seaweed Dictyota spiralis against both Leishmania amazonensis and Trypanosoma cruzi was evaluated in a previous study. Processing by bio-guided fractionation resulted in the isolation of three active compounds, classified as diterpenes. In the present study, we performed several assays to detect clinical features associated to cell death in L. amazonensis and T. cruzi with the aim to elucidate the mechanism of action of these compounds on parasitic cells. Methods The aims of the experiments were to detect and evaluate specific events involved in apoptosis-like cell death in the kinetoplastid, including DNA condensation, accumulation of reactive oxygen species and changes in ATP concentration, cell permeability and mitochondrial membrane potential, respectively, in treated cells. Results The results demonstrated that the three isolated diterpenes could inhibit the tested parasites by inducing an apoptosis-like cell death. Conclusions These results encourage further investigation on the isolated compounds as potential drug candidates against both L. amazonensis and T. cruzi. Graphic abstract

The Biodiversity of the Genus Dictyota: Phytochemical and Pharmacological Natural Products Prospectives

“…In vitro evaluation of the trypanocidal activity exhibited IC 50 values ranging from 13.11 to 35.28 µM for these compounds; in comparison to benznidazole, which was active with an IC 50 of 6.95 µM. Regarding cytotoxicity, CC 50 values were found to range from 36.96 µM for pachydictyol C (111) to 69.98 µM for 3,4-epoxy-7,18-dolabelladiene compared to miltefosine and benznidazole [126]. Diterpenes such as dictyol C (24), (8R,11R)-8,11-diacetoxypachydictyol A, (8R*,11R*)-6-O-acetyl-8-acetoxy-11-hydroxypachydictyol A, (8R*,11S*)-8-acetoxy-11hydroxypachydictyol A, and (8R*,11S*)-6-O-acetyl-8,11-dihydroxypachydictyol A, and a secohydroazulene derivative, named 7Z-7,8-seco-7,11-didehydro-8-acetoxypachydictyol A, were detected in Dictyota sp.…”

“…Dictyol B acetate (18) and dictyotadiol (118) (Figure 5) are diterpenes from D. dichotoma [62]. Sterols such as methyl-22-dehydrocholesterol, fucosterol (114), coprostanol (119), epicoprostanol (120), campesterol (121), stigmasterol (122), β-sitosterol (123), cholesterol (124), brassicasterol (125), cholestanol (126), and 5β-cholestan-3-one (127) (Figure 6) were discovered in the Malaysian D. dichotoma and tested for antifouling activity against Vibrio alginolyticus, V. mimicus, V. parahaemolyticus, P. aeruginosa, and B. subtilis. Coprostanol (119), epicoprostanol (120), campesterol (121), stigmasterol (122), and 5β-cholestan-3-one (127) (Figure 6) showed strong inhibition towards the selected bacterial strains, with IC 50 values ranging from 266.3 to 425.8 µg/mL, while fucosterol (114) gave no activity for all bacterial strains tested.…”

Gongolarones as antiamoeboid chemical scaffold

“…The graph represented in the Figs. [14][15][16] show the mean values of green fluorescence intensity produced by trophozoites of Acanthamoeba spp. Data indicated that the differences between the mean values of treated cells with compounds 1, 3 and 4, and negative controls cells were significant in all tested strains of Acanthamoeba; * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001.…”

“…Among these organisms, macroalgae contains a wide variety of bioactive secondary metabolites including phlorotannins, glycerols, quinones, polyketides, polysaccharide, diterpenoids, phenolic compounds, sterols, cyclic peptide, lipids, and alkaloids [13,14]. Lately, several reports have confirmed the diverse pharmacological properties of seaweeds as antimicrobial, anti-helminthic, cytotoxic, anti-inflammatory, and antiprotozoal among other biological activities [15][16][17].…”

Analysis of theLeishmania mexicanapromastigote cell cycle using imaging flow cytometry provides new insights into cell cycle flexibility and events of short duration

“…Propidium iodide (PI) quantitatively stains DNA (S2A,B Fig), but requires cell fixation, and is thus unsuitable for use in live cells. Hoechst 33342 is commonly used to stain the nucleus and kinetoplast in live Leishmania (40–42), but IFC indicated that it does not bind proportionally to DNA (S2C Fig). Images of Hoechst-stained cells revealed staining outside of the nucleus that may account for it being non-quantitative (S2C Fig).…”