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

Abstract

Triazole compounds have garnered significant interest due to their wide range of pharmacological activities 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 under 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 (Ki’s of 717.78 ± 3.40 to 122.57 ± 15.27 nM, 28.38 ± 7.78 to 132.04 ± 59.09 nM, 33.92 ± 1.91 to 138.13 ± 9.55 nM, and 0.095 ± 0.016 to 3.85 ± 0.82 μM for AChE, hCA I, hCA II, and ALR2, respectively). Additionally, in silico molecular docking studies were performed to validate the experimental results. 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. Therefore, they can be used as lead compounds for further research.