Two different families of N-oxide containing heterocycles were evaluated as in vitro growth inhibitors of T. cruzi. Both families of heterocycles were selected from our in-house library of compounds as analogues of active anti-T. cruzi N-oxide containing heterocycles. Derivatives from pyrimido[1,2-a]quinoxaline 6-oxide family were poorly active at the assayed doses. However, phenazine 5,10-dioxide derivatives displayed good to excellent anti-T. cruzi activities. The anti-T. cruzi activity of phenazine derivatives was related to substituent' electronic descriptors, sigma(p)(-). Derivatives 19, 20 and 23 were the most cytotoxic compounds against the protozoan and became excellent hit for further structural modifications.