Synthesis, Spectral Characterization and Molecular Docking Studies of Novel Benzidin-bis-tetrahydroacridine Analogues

Abstract

Alzheimer�s is a progresive neurodegenerative disease that interferes with human cognitive ability, memory and behavior. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes are major therapeutic routes for the treatment of Alzheimer disease. In the study, nevel bis-polymethylenquinoline-bis-carboxamides (3a-f) and bis-polymethylenquinoline-bis-carboxylic acids (5a-b) having as precursor benzidine, were obtained in good yields by Pfitzinger condensation reactions of bis-isatines with corresponding cyclanones. The compounds were characterized by elemental analysis, FT-IR, NMR and mass spectrometry. Furthermore, the compounds were subjected to molecular docking dynamics simulations to ascertain their potentials as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Molecular docking simulations showed varied binding activities towards the two binding sites of acetylcholinesterase: 4EY7 and 1OCD, and human butyrylcholinesterase: 1P0I. Compounds 3e and 5b demostrated strong binding affinities with 1P0I, 1OCD and 4EY7 biotargets similar to the binding modes of donepezil and tacrine (co-crystallized inhibitors of acetylcholinesterase) and butyrate (co-crystallized inhibitors of butyrylcholinesterase).