Thiosemicarbazones and thiadiazines derived from fluorinated benzoylthioureas: Synthesis, crystal structure and anti-Trypanosoma cruzi activity

Abstract A series of thiosemicarbazones was obtained by condensation of halogenated N -(diethylaminothiocarbonyl)benzimidoyl chlorides ( 3b–3h ) with 4,4-dimethyl-3-thiosemicarbazide. The activity of the halogenated compounds against the parasite Trypanosoma cruzi was evaluated and compared to the previously reported activity of the corresponding non-substituted thiosemicarbazone. It was found that the halogen-substitution enhances in most cases the anti-parasitic activity. The meta -fluorinated compound ( 4g ) was identified as the most potent one (IC 50 = 9.0 μM, CC 50 > 200 μM), having a selectivity index (SI = IC 50 /CC 50 ), which is 4-times higher than that of the non-substituted compound. Slight modification of the reaction conditions employed for the synthesis of some of the benzoylthioureas 3a–3g led to the unexpected formation of novel halogenated 6-amino-1,3,5-thiadiazine-2-thiones.