Abstract: | Three imidazole hydrazone compounds, namely 2‐(4‐nitro‐1H‐imidazol‐1‐yl)‐N′‐[1‐(pyridin‐2‐yl)ethylidene]acetohydrazide, C12H12N6O3, ( 1 ), 2‐(2‐nitro‐1H‐imidazol‐1‐yl)‐N′‐[1‐(pyridin‐2‐yl)ethylidene]acetohydrazide, C12H12N6O3, ( 2 ), and 2‐(2‐nitro‐1H‐imidazol‐1‐yl)‐N′‐[(phenyl)(pyridin‐2‐yl)methylidene]acetohydrazide, C17H14N6O3, ( 3 ), were obtained and fully characterized, including their crystal structure determinations. While all the compounds proved not to be cytotoxic to J774.A1 macrophage cells, ( 1 ) and ( 3 ) exhibited activity against Leishmania chagasi, whereas ( 2 ) was revealed to be inactive. Since both ( 1 ) and ( 3 ) exhibited antileishmanial effects, while ( 2 ) was devoid of activity, the presence of the acetyl or benzoyl groups was possibly not a determining factor in the observed antiprotozoal activity. In contrast, since ( 1 ) and ( 3 ) are 4‐nitroimidazole derivatives and ( 2 ) is a 2‐nitroimidazole‐derived compound, the presence of the 4‐nitro group probably favours antileishmanial activity over the 2‐nitro group. The results suggested that further investigations on compounds ( 1 ) and ( 3 ) as bioreducible antileishmanial prodrug candidates are called for. |