Effect of amidine derivatives on Leishmania amazonensis axenic amastigotes- Preliminary studies of structure-activity relationships

In a previous work, searching for new drugs with high efficiency and low to xicity, the in vitro antileishmanial activity of a series of seven amidine derivatives against Leishmania amazonensis promastigotes was reported. In o rder to compare the potential difference in the susceptibility between the two developmental stages of the parasite to these compounds, an analysis of the effects of these amidine derivatives on promastigotes and axenically g rown amastigotes of L. amazonensis was carried out. Among the N,N'-diphenyl -4-R-benzamidine (where R = H, Cl, Br, CN, NO2, CH3 and OCH3) derivatives s tudied, the most active compounds in both developmental stages were those w ith -Br, -Cl, -NO2, and -OCH3 substituents, the nonsubstituted ones being t he least active. However, the susceptibility to the drugs varied in these f orms, being higher in promastigotes. The electronic theoretical parameters calculated by molecular modelling using the semi-empirical AM1 method showe d good correlation with substituent constant (sigma (para), sigma (1) and F ). The chemical structure and biological activity relationships were invest igated in all compounds, although a small but significant correlation was o bserved. The obtained results suggest that other factors than the electroni c parameters have an influence on the biological response.