Structural studies and antileishmanial activity of 2‐acetylpyridine and 2‐benzoylpyridine nitroimidazole‐derived hydrazones

Three imidazole hydrazone compounds, namely 2‐(4‐nitro‐1 H ‐imidazol‐1‐yl)‐ N ′‐[1‐(pyridin‐2‐yl)ethylidene]acetohydrazide, C 12 H 12 N 6 O 3 , ( 1 ), 2‐(2‐nitro‐1 H ‐imidazol‐1‐yl)‐ N ′‐[1‐(pyridin‐2‐yl)ethylidene]acetohydrazide, C 12 H 12 N 6 O 3 , ( 2 ), and 2‐(2‐nitro‐1 H ‐imidazol‐1‐yl)‐ N ′‐[(phenyl)(pyridin‐2‐yl)methylidene]acetohydrazide, C 17 H 14 N 6 O 3 , ( 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.