Cytotoxicity of Hydrazones of Morpholine Bearing Mannich Bases Towards Huh7 and T47D Cell Lines and Their Effects on Mitochondrial Respiration

N,N'-bis[1-(substitutedphenyl)-3-(morpholine-4-yl) propylidene] hydrazine dihydrochlorides, N1-N11 were designed and synthesized as cytotoxic agents. These compounds were synthesized by the reaction of 2 moles of 1-( substitutedphenyl)-3-(morpholine-4-yl)-1-propanone hydrochlorides with 1 mole of hydrazine hydrate. The compounds reported here are new, except N1 and N4. The cytotoxicity of the compounds was tested against human hepatoma (Huh7) and breast cancer (T47D) cell lines. 5-Fluorouracil (5-FU) was used as a reference compound. It was found that N3, which has 4-methoxy substituent on phenyl ring, was the most cytotoxic compound towards both cell lines. Its cytotoxicity was 5.6 times higher than 5-FU. Representative compounds N2 at 144, 264 and 424 mu M and N3 at 401 mu M concentrations significantly inhibited mitochondrial respiration in a dose dependent manner in liver homogenates. This suggests that the inhibition of mitochondrial respiration may be one of the contributing mechanisms to the cytotoxicity of the compounds. N3 may serve as a candidate compound for further studies.