Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative

Abstract EN

The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease.

Therefore, new therapeutical options are mandatory.

In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, against Trypanosoma cruzi forms.

LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50 = 259.4±6.1 μM) and intracellular amastigotes infecting peritoneal macrophages (IC50 = 188.2±47.5 μM), with no harmful effects upon the mammalian cells (CC50 values greater than 4 mM), resulting in a high selectivity index (CC50/IC50 > 20).

Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC50 of about 191.8±10.5 μM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50 of 255.1±3.6 μM.

Finally, we investigated the mutagenic potential of the nitrone by the Salmonella/microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 μM.

Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms of T.

cruzi, offering new insights into CD treatment suggesting additional in vivo tests.