In vitro leishmanicidal activity of dihydroquinoline lactones

A series of dihydroquinoline lactones derivatives 4ae-be were synthesized from a MW assistedmulticomponent reaction between tetronic acid (1), anilines 2a-b and aromatic aldehydes 3a-e, in H2O for 15 min (Scheme 1). These compounds were initially subjected to screening for in vitro leishmanicidal activity against the promastigote form of Leishmania amazonensis in concentration of 50 μg/mL. Screening results indicate that all of the synthesized compounds were actives. However, only compounds with parasite lysis higher than 80% were evaluated at lower concentrations for IC50 determination. The cytotoxic concentration (CC50) of the more actives compounds (IC50 < 4.0 μg/mL) was also determinate on macrophage peritoneal. Compounds 4ac e 4be were more potent than other derivative with IC50 value of 2.61 μg/mL and 3.57 μg/mL, respectively, and selectivity indexes (SI) 29.7 and 20.4 fold higher than those of the reference drug amphotericin (Table 1). The presence of the nitro group allied to the methylenedioxy group in benzylic ring in 4be increased the selectivity index, as evidenced by the much lower selectivity index of the parent compound 4bd. Regarding 4aa and 4ac, the presence of the CF3 group, smaller and more lipophilic, favored the increase of the selectivity index to 4ac. The experimental data suggest that these compounds may be further investigated as possible targets for development of new drug for treatment of cutaneous leishmaniosis.