Tambjamines and Prodiginines: Biocidal Activity against Trypanosoma cruzi

Abstract

The aim of this work was to explore new therapeutic options against Chagas disease by the in vitro analysis of the biocidal activities of several tambjamine and prodiginine derivatives, against the Trypanosoma cruzi CLB strain (DTU TcVI). The compounds were initially screened against epimastigotes. The five more active compounds were assayed in intracellular forms. The tambjamine MM3 and both synthetic and natural prodigiosins displayed the highest trypanocidal profiles, with IC50 values of 4.52, 0.46, and 0.54 µM for epimastigotes and 1.9, 0.57, and 0.1 µM for trypomastigotes/amastigotes, respectively. Moreover, the combination treatment of these molecules with benznidazole showed no synergism. Finally, oxygen consumption inhibition determinations performed using high-resolution respirometry, revealed a potent effect of prodigiosin on parasite respiration (73% of inhibition at ½ IC50), suggesting that its mode of action involves the mitochondria. Moreover, its promising selectivity index (50) pointed out an interesting trypanocidal potential and highlighted the value of prodigiosin as a new candidate to fight Chagas disease.

Prodigiosin: a promising biomolecule with many potential biomedical applications

“…There is wide experimental evidence of the potential use of PG against neglected diseases, such as Chagas disease, amebiasis, and malaria [ 84–86 ]. It was suggested that the mechanism by which PG may act is by triggering mitochondrial dysfunction.…”

Discovery and Optimization of Tambjamines as a Novel Class of Antileishmanial Agents

“…24−26 In addition, these natural and synthetic compounds have been extensively investigated for various therapeutic applications, including antimicrobial, 27−29 anticancer, 30−35 antitumor, 27,29,36 and immunosuppressive 37 activities with various MoA. 38−41 Indeed, a recent study demonstrated the effectiveness of both TAs and PGs against the kinetoplastid parasites such as Trypanosoma cruzi, 42 the causative agent of Chagas disease. To the best of our knowledge, the exact MoA are unknown for these novel TA chemotypes; however, they likely induce mitochondrial swelling and lysosomal dysfunction leading to autophagy and necrotic cell death in cancer cells.…”

Formulation and evaluation of anion transporters in nanostructured lipid carriers

“…3–5 In particular, potential applications of these compounds as antimicrobial, antiparasitic or anticancer agents have been reported. 6–10 Applications as transmembrane protein surrogates as potential candidates for the treatment of diseases caused by defective transmembrane anion transport, like cystic fibrosis, have also been explored. 11,12…”