Synthesis of pyrrole-heterocyclic derivatives as anti-Alzheimer and antidiabetic candidates: An in vitro-in silico study

In this study, pyrrole-based heterocyclic compounds (2a-k) were synthesized and characterized by elemental analysis, IR and NMR spectra. 11 representatives of the pyrrole derivatives were chosen as objects for the studying biological activity. Among them were the ensembles of pyrroles with other pharmacologically active heterocycles, such as pyridines, aminopyrimidines, benzo[b][1,4]diazocin-2(1H)-ones, and fused pyrrole compounds, namely pyrrolo[1′,2′:3,4]imidazo[1,2-a]pyridines. The compounds 2c, 2e, and 2k were synthesized for the first time in this study. This assessment focused on their inhibitory potential against acetylcholinesterase (AChE) and α-glycosidase (α-Gly) enzymes. Among the studied compounds, 4-[5-(4-fluorophenyl)-1-vinyl-1H-pyrrol-2-yl]-6-phenylpyrimidin-2-amine (2e) and 4-[5-(4-fluorophenyl)-1H-pyrrol-2-yl]-6-phenylpyrimidin-2-amine (2f) emerged as leading candidates, demonstrating potent inhibition against AChE and α-glycosidase enzymes with favorable pharmacokinetic profiles. AChE was most effectively inhibited by compounds of 2f and 2i (Ki: 4.50 ± 0.16 and 6.01 ± 0.15 nM). The results from biological activities, molecular docking, dynamics simulations, and ADME predictions collectively highlight the potential of these compounds to be an inhibitor candidate for AChE and α-Gly.