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Design, Synthesis and Biological Evaluation of Some Novel 3-Methlyquinoxaline-2-Hydrazone Derivatives

Taiwo FO, Obuotor EM, Olawuni IJ, Ikechukwu DA and Iyiola TO

Alzheimer’s disease is a chronic and progressive neurodegenerative disease which occurs due to lower levels of acetylcholine neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetylcholinesterase and butyrylcholinesterase have been reported to be the primary regulators of the acetylcholine levels in the brain. Evidence shows that acetylcholinesterase activity decreases in Alzheimer’s disease, while activity of butyrylcholinesterase elevate in advanced Alzheimer’s disease, which suggests a key involvement of butyrylcholinesterase in acetylcholine hydrolysis during Alzheimer’s disease symptoms. In order to sustain the level of remaining acetylcholine, acetylcholinesterase and butyrylcholinesterase inhibitors may be used. Therefore, inhibiting the activity of butyrylcholinesterase may be an effective way to control Alzheimer’s disease associated disorders. In this study, eleven 3-methylquinoxaline-2-hdrazones were synthesized from the reactions of 3-methylquinoxaline-2-hydrazine with different substituted aromatic ketones and aromatic aldehyde. All the newly synthesized compounds have been characterized on the basis of IR, 1H-NMR and 13H-NMR spectral data as well as physical data. All the synthesized compounds were biologically evaluated against cholinesterases (acetylcholinesterase and butyrylcholinesterase). Compounds 2-12 were found to be a good selective inhibitor for acetycholinesterase and butyrylcholinesterase. Among the series, compounds 6 (IC50=170 ± 30 μg/mL) and 10 (IC50=180 ± 10 μg/mL) were found to be the most active inhibitors against acetylcholinesterase, while compounds 2 (IC50=780 ± 10 μg/mL), 5 (IC50=550 ± 10 μg/mL) and 6 (IC50=790 ± 10 μg/mL), were found to be most active inhibitor against butyrylcholinesterase. The IC50 values for all the synthesized compounds were lower than standard, eserine (IC50=70 ± 20 μg/mL). Their considerable acetylcholinesterase and butyrylcholinesterase inhibitory activities makes them a good candidate for the development of selective acetycholinesterase and butyrylcholinesterase inhibitors.