Synthesis and Biological Activities of New N-(benzylidene)-3-cyclohexylpropionic Acid Hydrazide Derivatives

The hydrazones constitute an important class of biologically active drug molecules that have attracted the attention of medicinal chemists due to their wide-ranging pharmacological properties since decades. In this present study, 10 new N-(benzylidene)-3-cyclohexylpropionic acid hydrazide derivatives were synthesized. The reaction of 3-cyclohexylpropionic acid hydrazide with various benzaldehydes resulted in their derivatives. The chemical structures of the compounds were elucidated by spectroscopic techniques such as IR, ¹H-NMR and FAB⁺-MS and elemental analyses. The series of compounds were evaluated comparatively for their antiinflammatory, antifungal and cytotoxic activities. Antiinflammatory activity was determined in terms of inhibition of NF-κB, ROS generation and iNOS activity. Several derivatives inhibited NF-κB and iNOS, but no effect was observed on intracellular ROS generation and no cytoxicity was observed. Furthermore, the antifungal activity of hydrazide derivatives was evaluated by bioautography and a broth microdilution assays against plant pathogens. In-depth dose response studies at micromolar concentration showed that hydrazide derivatives were more active against Phomopsis obscurans and P. viticola than the other tested fungi. The results of the biological evaluations compared with the chemistry suggested that different groups on the phenyl ring influenced the physicochemical properties and thus the contributed to the biological activity.