Novel propanolamine derivatives attached to 2-metoxifenol moiety: Synthesis, characterization, biological properties, and molecular docking studies

Abstract

The synthesis of seven new beta-amino alcohols was designed and performed by starting from eugenol, a natural phenolic compound known to be biologically active. The synthesized compounds were obtained in yields ranging from 54 to 81%. Molecule structures were determined with FT-IR, H-1 NMR and C-13 NMR spectroscopies. In addition, the inhibitory effects of these substances on acetylcholinesterase (AChE), alpha-glycosidase (alpha-Gly), human carbonic anhydrase I (hCA I), and human carbonic anhydrase II (hCA II) enzymes have been investigated. It has been seen that all compounds have a better ability to inhibit compared to existing tried inhibitors. Among these, the best inhibitor against AChE enzyme is 2b (Ki 62.08 +/- 11.67 mu M and IC50 90.33), and against alpha-Gly, 2c showed the highest effect (Ki 0.33 +/- 0.08 mu M and IC50 0.28). The best inhibitor against hCA I, and hCA II enzymes is compound 2f. For hCA I and hCA II, Ki value was measured as 9.68 +/- 1.32 and 11.46 +/- 2.64 mu M and IC50 values as 7.37 and 8.26 mu M respectively. The interactions of the studied new propanolamine derivatives with the enzymes were done by molecular docking calculations and their biological activities were compared to the experimental tests. Studied enzymes in molecular docking calculations are acetylcholinesterase (AChE) is PDB ID: 4M0E, alpha-glycosidase (alpha-Gly) is PDB ID: 1R47, human carbonic anhydrase isoenzyme I (hCA I) PDB ID: 3LXE is human carbonic anhydrase isoenzyme II (hCA II) is PDB ID: 5 AML.