| Affiliation: | 1. Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan;2. Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkey;3. Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, Gaziantep, Turkey Department of Bioinformatics and Computational Biology, Institute of Health Sciences, Gaziantep University, Gaziantep, Turkey;4. Department of Molecular Biology and Genetics, Faculty of Science, Bartin University, Bartin, Turkey;5. Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan;6. Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, Egypt;7. Department of Physics, University of Sargodha, Sargodha, Pakistan;8. Department of Chemistry, Govt. Post-Graduate Gordon College, Rawalpindi, Pakistan;9. Chemistry Department, Faculty of Science, Menoufia University, Menoufia, Egypt |
| Abstract: | A series of xanthene-based thiazoles was synthesized and characterized by different scpectroscopic methods, i.e. Proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR), infrared spectroscopy, carbon hydrogen nitrogen analysis, and X-ray crystallography. The inhibition potencies of 18 newly synthesized thiazole derivatives were investigated on the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase (α-Amy), and α-glycosidase (α-Gly) enzymes in accordance with their antidiabetic and anticholinesterase ability. The synthesized compounds have the highest inhibition potential against the enzymes at low nanomolar concentrations. Among the 18 newly synthesized molecules, 3b and 3p were superior to the known commercial inhibitors of the enzymes and have a much more effective inhibitory potential, with IC50: 2.37 and 1.07 nM for AChE, 0.98 and 0.59 nM for BChE, 56.47 and 61.34 nM for α-Gly, and 152.48 and 124.84 nM for α-Amy, respectively. Finally, the optimized 18 compounds were subjected to molecular docking to describe the interaction between thiazole derivatives and AChE, BChE, α-Amy, and α-Gly enzymes in which important interactions were monitored with amino acid residues of each target enzyme. |
