Novel pyrrole based triazole moiety as therapeutic hybrid: synthesis, characterization and anti-Alzheimer potential with molecular mechanism of protein ligand profile

Abstract

As a springboard to explore novel potent inhibitors of cholinesterase enzymes (AChE and BChE) responsible for causing Alzheimer disorder, the current study was conducted to synthesize pyrrole derived triazole based Schiff base scaffolds by facile synthetic route. These compounds were validated by 1 HNMR, 13 CNMR and HREI-MS. All these scaffolds (1–16) were examined for their inhibitory activity against AChE and BChE in contrast to Donepezil ( 10.20 ± 0.10 and 10.80 ± 0.20 µM ) and Allanzanthone ( 12.40 ± 0.10 and 13.10 ± 0.10 µM ). All pyrrole derived triazole based Schiff base scaffolds (1–16) showed varied range of inhibitory potentials against acetylcholinesterase and butyrylcholinesterase enzymes with lowest inhibition concentration values ranging from 5.10 ± 0.40–27.10 ± 0.10 µM (for AChE) and 5.60 ± 0.30–28.40 ± 0.30 µM (for BChE). SAR analysis of these derivatives revealed analog 7 as lead molecule against targeted enzyme, while analog 6 and 11 were ranked as second and third most potent scaffolds. Binding affinity and selectivity of potent molecules against targeted enzymes were examined by molecular docking and obtained results showed that potent molecule have versatile significant binding interactions with stated enzymes. Furthermore, safety profiles of potent analogues were predicted via ADMET protocols. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s13065-024-01340-x.