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Abstract

DESIGN, SYNTHESIS AND EVALUATION OF p-AMINOBENZOIC ACID AND 4-AMINOPYRIDINE ANALOGUES AS CHOLINESTERASE INHIBITORS FOR MANAGEMENT OF ALZHEIMER’S DISEASES

Shashi Kant Singh, Saurabh K. Sinha and Mrunal K. Shirsat*

Abstract

Some new Schiff bases of p-aminobenzoic acid and semicarbazones of 4-aminopyridine has been designed, synthesized, characterized by analytic methods such as UV, IR, NMR, elemental analysis and evaluated for cognition enhancing activities through the inhibition of acetylcholinesterase (AChE) by applying the molecular docking studies, performed enzyme kinetics study by Ellman’s spectrophotometric method and by passive avoidance model. The results illustrated a significant cognition enhancing effect on passive avoidance test with a significant reversal of scopolamine-induced amnesia, which is comparable with standard drug rivastigmine. The in-vitro study of synthesized compounds showed maximum activity of compound-2 and 5 compared to standard drug rivastigmine, whereas its enzyme kinetic study revealed a non-competitive inhibition of acetylcholinesterase (AChE), which may be attributed to a possible interaction of compound with the peripheral anionic site (PAS) of AChE and was also confirmed by molecular docking studies.

Keywords: P-Aminobenzoic Acid, 4-Aminopyridine, Acetylcholinesterase, Passive Avoidance Test, Rivastigmine.


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