Synthesis and 2D-QSAR study of dispiropyrrolodinyl-oxindole based alkaloids as cholinesterase inhibitors

In this work, we describe the regioselective synthesis of some new dispiro [indene-2,3'-pyrrolidine-2',3 ''-indoline]-1,2 ''(3H)-dione 4-29 attributable to the previously described methods. All the new chemical entities were assessed in-vitro as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes; while no significant inhibitory activity for the tested compounds were assigned on AChE, compounds 4, 27, 29, 28 and 15 were the most active against BChE enzyme with IC50 = 13.7 mu M, 21.8 mu M, 22.1 mu M, 22.9 mu M and 24.9 mu M respectively compared to Donepezil (IC50 = 0.72 mu M). Compound 4 was found to have a mixed type mode of inhibition, the bioactivity of the new chemical entities (N = 26, n = 5, R-2 = 0.893, R-2 cvOO = 0.831, R-2 cvMO = 0.838, F = 33.32, s(2) = 0.003) was elucidated via a statistically significant QSAR model utilizing CODESSA-Pro software that validated the observed results.