Design and Synthesis of 4-amino-1H-indole-6-carboxamide derivatives as targeting molecules of Cholinesterase Enzymes
DOI:
https://doi.org/10.5281/zenodo.21236265Keywords:
Tacrine, Alzheimer’s disease, cholinesterase inhibitors, Hydrazine.Abstract
Alzheimer’s disease, being a neurodegenerative disorder that progresses over time, is one of such diseases that needs immediate and serious attention. As inhibitors of acetylcholinesterase and butyrylcholinesterase for the treatment of Alzheimer’s disease, a new series of 4-amino-1H-indole-6-carboxamides has been designed, and 15 such molecules have been synthesized from 3,5-dinitrobenzoic acid via a multicomponent reaction. These synthesized compounds were characterized by spectral data and evaluated for inhibitory activity againstacetylcholinesterase and butyrylcholinesterase. Among the series compound 9o with indole carboxamide fused with trimethoxy benzaldehyde with methylene-2-(thiazol-4-yl) aceto hydrazide linker showed potent inhibitory activity with IC50 of 0.94±0.10 and 1.10 ±0.05 μM compared to standard drug rivastigmine 0.47 ±0.2 & 0.65 ±0.02 μM against AChE and BuChE, respectively. 9o was further studied for brain cholinesterase inhibitory activity and exhibited potent activity with IC50 values of 25.32±0.25 and 28.24±0.18μM, respectively. Docking studies revealed that the designed molecules interacted with the nicotinic receptor through at least two hydrogen-bond interactions, except for a few compounds.
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