Phenotypic Analysis of the Anti-T. cruzi Activity of Natural Products Obtained from Brazilian Botanical Sources

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects more than 6 million people worldwide, predominantly in Latin America. Current chemotherapy relies on Benznidazole (Bz) and Nifurtimox, which are associated with adverse effects and limited efficacy during chronic infection, underscoring the need for new therapeutic options. Natural products remain an important source of bioactive molecules for antiparasitic drug discovery. In this study, 34 extracts obtained from 18 Brazilian plant species were evaluated for anti-T. cruzi activity. After cytotoxicity assessment, extracts were screened against intracellular amastigotes (Tulahuen strain, DTU VI) and bloodstream trypomastigotes (Y strain, DTU II). Most samples exhibited low toxicity toward mammalian cells (LC50 > 120 μg/mL). Among them, the inflorescence extract of Piper claussenianum (Miq.) C. DC. (PCFLD) showed the highest activity. At 20 μg/mL, PCFLD reduced intracellular parasite burden by 94%, with an EC50 of 3.6 ± 0.36 μg/mL and a selectivity index of 20. Against trypomastigotes, the extract displayed an EC50 of 11.56 ± 5.88 μg/mL and a selectivity index of 11. In an acute murine model, PCFLD (10 mg/kg/day) reduced peak parasitemia by 40%, outperforming Bz at the same dose. These findings identify P. claussenianum as a promising source of anti-T. cruzi compounds.