Design, synthesis, biological evaluation and molecular docking studies of novel 1H-1,2,3-Triazole derivatives as potent inhibitors of carbonic anhydrase, acetylcholinesterase and aldose reductase

Triazole compounds have garnered significant interest due to their wide range of pharmacological activi-ties and ease of synthesis. Click chemistry is a synthetic method frequently used in triazole synthesis. In this study 1H-1,2,3-triazole was synthesized by the Banert cascade reaction using click chemistry. A dozen novel substituted 1H-1,2,3-triazole derivatives were synthesized using an efficient synthetic method un-der mild conditions. The inhibitory effects of these compounds on the activity of acetyl cholinesterase (AChE), human carbonic anhydrase (hCA) I and II, and aldose reductase (ALR2) were evaluated. The 1H- 1,2,3-triazole compounds were determined to be highly potent inhibitors of AChE, hCA I and II, and ALR2 (K-i's of 717.78 & PLUSMN; 3.40 to 122.57 & PLUSMN; 15.27 nM, 28.38 & PLUSMN; 7.78 to 132.04 & PLUSMN; 59.09 nM, 33.92 & PLUSMN; 1.91 to 138.13 & PLUSMN; 9.55 nM, and 0.095 & PLUSMN; 0.016 to 3.85 & PLUSMN; 0.82 mu M for AChE, hCA I, hCA II, and ALR2, respec-tively). Additionally, in silico molecular docking studies were performed to validate the experimental re-sults. Compounds 51 and 58 with the best activities with AChE, hCA I, hCA II and ALR2 were studied by molecular docking. These compounds showed similar or better interactions with reference drugs. There-fore, they can be used as lead compounds for further research.(c) 2022 Published by Elsevier B.V.

Automated summary

Triazole compounds, synthesized using click chemistry in this study, exhibited potent inhibitory effects on AChE, hCA I and II, and ALR2. Several novel substituted 1H-1,2,3-triazole derivatives were synthesized under mild conditions. In silico molecular docking studies confirmed the experimental results and identified lead compounds with strong interactions.