Anticholinesterase activity of β-carboline-1,3,5-triazine hybrids

Abstract

The β-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC 50 values in the range from 1.0-18.8 µM being obtained. The N-{2- [(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-β-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine.

Recent biological applications of heterocyclic hybrids containing s-triazine scaffold

“…Carboline has three fused ring structures with nitrogen as a heteroatom. The molecular hybrids of s -triazine and carboline ( 71 ) 85 were prepared through a linker approach in good yield and screened in vitro against cholinesterase enzymes (acetyl and butryl). The IC 50 value of these compounds ranged between 1.0 and 18.8 μM with the lowest value of 1.0 ± 0.1 μM which is more efficient than the standard drug Donepezil, IC 50 = 2.9 ± 0.5 μM.…”