3-(1H-pyrazole-1-yl/1H-1,2,4-triazole-1-yl)-N-propananilide Derivatives: Design, Synthesis and Neuroprotectivity Potential Against 6-OHDA Induced Neurotoxicity Model.

Objectives: Excessive amounts of neuroapoptosis are the underlying cause of neurodegenerative diseases. Bax is a pro-apoptotic member of the B-cell lymphoma-2 family that activates caspases which are the members of the cysteine protease family that play a significant role in the initiation and execution phases of apoptosis. The aim of this study was to design and synthesize a group of N-propananilide derivatives bearing pyrazole or 1,2,4-triazole ring were designed and synthesized to analyze the neuroprotectivity potential against 6-hydroxy-dopamine (6-OHDA). Four compounds possessed protectivity at lower doses were subjected to further studies on caspase-3 and Bax pathway. Materials and Methods: Designed compounds were synthesized by reacting 1H-pyrazole or 1H-1,2,4-triazole with propananilide intermediates in Dimethylformamide. The neuroprotective activity of the title compounds was analyzed against 6-OHDA-6-OHDA-induced neurotoxicity model. Then, caspase-3 and Bax levels were determined for the selected compounds by Western blot study. Results: All twelve 3-(1H-pyrazole-1-yl/1H-1,2,4-triazole-1-yl)-N-propananilide derivatives possessed neuroprotectivity against the 6-OHDA-induced neurotoxicity model ( Conclusion: All designed and synthesized derivatives possessed neuroprotectivity against 6-OHDA-induced neurotoxicity in the SH-SY5Y cell line and compounds 7, 10, 11, and 12 revealed that their neuroprotectivity originated from the decreasing Bax expression levels and caspase-3 activation.