Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors

Abstract

We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3-triazole derivatives a Cu(i)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. The newly synthesized compounds were evaluated for their inhibition activity against acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound exhibited potent inhibition against AChE and BChE with IC values of 4.89 μM and 3.61 μM, respectively. Further structure-activity relationship (SAR) and molecular modeling studies may provide valuable insights into the design of better tacrine-triazole analogues with potential therapeutic applications for AD.

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

“…To target Alzheimer's disease, the inhibitory effects of a series of novel tacrine-1,2,3-triazole compounds were investigated on Electrophorus electricus AChE and horse serum BChE. 144 Among the synthesised derivatives, hybrid 115 (Fig. 14) strongly inhibited AChE (75%) and BChE (90%) with IC 50 values of 4.89 and 3.61 µM at a concentration of 100 µM, respectively.…”

Metal‐Free, Visible‐Light Promoted Intramolecular Azole C−H Bond Amination Using Catalytic Amount of I2: A Route to 1,2,3‐Triazolo[1,5‐a]quinazolin‐5(4H)‐ones

“…[1] Among various kinds of fully substituted 1,2,3-triazoles, heterocyclic systems fused with a 1,2,3-triazole ring have been widely studied because of their increasing applications in drug discovery and chemical biology. [2] Therefore, the development of synthetic protocols for the effectively access of 1,2,3-triazolobenzo-heterocycles has drawn intensive attention to synthetic chemists and several types of privileged 1,2,3-triazole polycyclic compounds have been successfully synthesised. [3] 1,2,3-Triazolo [1,5-a]quinazolin-5(4H)-ones are an unique class of N-heterocycles that unified two pharmaceutical important scaffolds, 1,2,3-triazole and quinazolin-4 (3H)-one, [4] into a single molecule.…”

Discovery of novel 1,4-disubstituted 1,2,3-triazole phenylalanine derivatives as HIV-1 capsid inhibitors

“…Furthermore, the triazole has two H-bond acceptors, which provides potential additional interactions with the surrounding residues through H-bonding, p-p stacking, and dipole interaction. [28][29][30] Besides, the application of the Cu(I)catalyzed azide and alkyne 1,3-dipolar cycloaddition (CuAAC), oen referred to as the "click reaction", makes it convenient to synthesize 1,4-disubstituted triazole. [31][32][33] In this study, we continued to design and synthesize 51 other 1,2,3-triazole phenylalanine derivatives divided into three sub-series, to enrich structure-activity relationships (SARs).…”