In Vitro and In Vivo Studies of the Trypanocidal Activity of Four Terpenoid Derivatives against Trypanosoma cruzi

Abstract

Abstract. Four terpenoid derivatives were examined for their activity against Trypanosoma cruzi. Our results show that two compounds were very active in vitro against both extra-and intracellular forms. These compounds, non-toxic for the host cells, are more effective than the reference drug benznidazole. The capacity to infect cells was negatively affected and the number of amastigotes and trypomastigotes was reduced. A wide range of ultrastructural alterations was found in the epimastigote forms treated with these compounds. Some metabolic changes occurred presumably at the level of succinate and acetate production, perhaps caused by the disturbance of the enzymes involved in sugar metabolism inside the mitochondria. In vivo results were consistent with those observed in vitro. The parasitic load was significantly lower than in the control assay with benznidazole. The effects of these products showed the reduction of the anti-T. cruzi antibodies level during the chronic stage.

Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids

“…Among the natural compounds, terpenoids display a wide range of biological activities such as anticancer and anti-inflammatory actions and are effective against infective agents such as viruses, bacteria and parasites [10], [11]. Several terpenoids have been reported to have trypanocidal and leishmanicidal activities [12]–[15]. Recent research has shown the potential role of terpenoids as promising compounds against neglected protozoan diseases such as Chagas' disease and leishmaniasis [16], [17].…”

Applicability of plant-based products in the treatment ofTrypanosoma cruziandTrypanosoma bruceiinfections: a systematic review of preclinicalin vivoevidence

“…2015) and terpenoids (Ramírez-Macías et al . 2012; Lozano et al . 2016) were the main classes of secondary metabolites associated with antitrypanosomal activity in both diseases.…”

Anti-Trypanosoma Activity and Synergistic Effects of Natural and Semi-Synthetic Triterpenes and Predominant Cell Death through Autophagy in Amastigote Forms

“…The oxidation yield was 97%; 13 3-O-Succinyl-11-oxo-α/β-amyrin (7) A solution of 3-O-succinyl-α/β-amyrin (0.20 g, 0.380 mmol), acetic anhydride (3 mL) and acetic acid tert-butyl chromate (3 mL) was refluxed for 6 h. The mixture was concentrated and subjected to liquid-liquid extraction with CH 2 Cl 2 /H 2 O and oxalic acid (5%). The oxidation yield was 97%; 3-O-Phthaloyl-11-oxo-α/β-amyrin (8) To obtain the solution of 3-O-phthaloyl-11-oxo-α/β-amyrin (8), acetic anhydride (3 mL) and acetic acid tert-butyl chromate (3 mL) were added in the 3-O-phthaloyl-α/β-amyrin (0.20 g, 0.348 mmol), and refluxed for 6 h. Then, the mixture was concentrated and subjected to liquid-liquid extraction with CH 2 Cl 2 /H 2 O and oxalic acid (5%).…”

“…Then, isopropanol (2 mL) was added and, after 10 min, the product was washed with aqueous solution of oxalic acid (10%, 3 × 10 mL) and water (3 × 10 mL), dried with sodium sulfate (Na 2 SO 4 ) and the solvent evaporated, under vacuum. The product (85 mg) was subjected to separation by semi-preparative HPLC, thus obtaining a white solid (10 mg), which was characterized as lup-20(29)-en-3-one; 13 C NMR (100 MHz, CDCl 3 ) was compared with literature data. Betulinic acid (11) This natural compound was previously isolated and characterized by our collaborator from Gustavia augusta L. (Lecythidaceae family) and provided a sample to this study.…”

“…Furthermore, different classes of terpenes have been demonstrated desirable synergistic effects when combined, since drug combination may improve the parasitic activity with lower dosage of these substances, in addition to reducing their undesirable toxic effects. [11][12][13][14][15][16][17] The search for synergic compounds can improve the efficiency of the treatment, reduce their toxicities on mammalian cells and diminish the selection of resistant mutations. 12,[18][19][20] Alternative strategies have been designed to identify candidates among the already available drugs in the market that could be used in combination to provide synergic effects and improve the chemotherapy efficacy.…”