Vanillin derivatives as antiamnesic agents in scopolamine-induced memory impairment in mice

Abstract

Amnesia is a major health problem prevalent in almost every part of the world specifically in old age peoples. Vanillin analogues have played an important role in the field medicines. Some of them have been documented to be promising inhibitors of cholinesterases and could therefore, be used as antidepressant, anti-Alzheimer and as neuroprotective drugs. In this connection, the present study was designed to synthesize new vanillin analogues (SB-1 to SB-6) of varied biological potentials. The synthesized compounds were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and as scavengers of DPPH and ABTS free radicals followed by behavioural antiamnesic evaluation in mice. The compounds; SB-1, SB-3, SB-4 and SB-6 more potently inhibited AChE with IC50 values of 0.078, 0.157, 0.108, and 0.014 μM respectively. The BChE was more potently inhibited by SB-3 with IC50 of 0.057 μM. Moreover, all of the tested compounds exhibited strong antioxidant potentials with promising results of SB-3 against DPPH with IC50 of 0.305 μM, while SB-5 was most active against ABTS with IC50 of 0.190 μM. The in-vivo studies revealed the improvement in memory deficit caused by scopolamine. Y-Maze and new object recognition test showed a considerable decline in cognitive dysfunctions. In Y-Maze test the spontaneous alteration of 69.44 ± 1% and 84.88 ± 1.35% for SB-1 and 68.92 ± 1% and 80.89 ± 1% for SB-3 at both test doses were recorded while during the novel object recognition test the Discrimination Index percentage of SB-1 was more pronounced as compared to standard drug. All compounds were found to be potent inhibitors of AChE, BChE, DPPH, and ABTS in vitro however, SB-1 and SB-3 were comparatively more potent. SB-1 was also more active in reclamation of memory deficit caused by scopolamine. SB-1 and SB-3 may be considered as excellent drug candidates for treating amnesia subjected to toxicological evaluations in other animal models.