Thio- and selenosemicarbazones as antiprotozoal agents against <i>Trypanosoma cruzi</i> and <i>Trichomonas vaginalis</i>

Abstract

Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1 and N-4 and the nature of the chalcogen atom (S, Se). These compounds were evaluated towards <i>Trypanosoma cruzi</i> and <i>Trichomonas vaginalis</i>. Thiosemicarbazide <b>31</b> showed the best trypanocidal profile (epimastigotes), similar to benznidazole (BZ): IC₅₀ (<b>31</b>)=28.72 μM (CL-B5 strain) and 33.65 μM (Y strain), IC₅₀ (BZ)=25.31 μM (CL-B5) and 22.73 μM (Y); it lacked toxicity over mammalian cells (CC₅₀ > 256 µM). Thiosemicarbazones <b>49</b>, <b>51</b> and <b>63</b> showed remarkable trichomonacidal effects (IC₅₀=16.39, 14.84 and 14.89 µM) and no unspecific cytotoxicity towards Vero cells (CC₅₀ ≥ 275 µM). Selenoisosters <b>74</b> and <b>75</b> presented a slightly enhanced activity (IC₅₀=11.10 and 11.02 µM, respectively). Hydrogenosome membrane potential and structural changes were analysed to get more insight into the trichomonacidal mechanism.