Benzoxazole based thiazole hybrid analogs: Synthesis, in vitro cholinesterase inhibition, and molecular docking studies

• Published in: Computational toxicology Vol. 25; p. 100253
• Main Authors: Hussain, Rafaqat, Rahim, Fazal, Rehman, Wajid, Adnan Ali Shah, Syed, Khan, Shoaib, Khan, Imran, Rasheed, Liaqat, Imran, Syahrul, Wadood, Abdul, Abdellatif, Magda H.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.02.2023
• Subjects: 1,3-Thiazole; Benzoxazole; Cholinesterase inhibitors; Molecular docking; SAR; Synthesis; Synthesis; SAR; Cholinesterase inhibitors; Molecular docking; Benzoxazole; 1,3-Thiazole
• ISSN: 2468-1113; 2468-1113
• DOI: 10.1016/j.comtox.2022.100253

Acetylcholinesterase and butyrylcholinesterase enzymes are therapeutic target for Alzheimer disease and their inhibitors play a vital role for the treatment of this disease. A new series of benzoxazole based 1,3-thiazole hybrid scaffolds (1–20) were synthesized and assessed for acetylcholinesterase and butyrylcholinesterase inhibition profile and then characterized by using different spectroscopic tools such as 1H NMR, 13C NMR and HREI-MS spectroscopy. Four scaffolds such as 1, 4, 12 and 19 showed AChE potency almost comparable to standard drug having IC50 values 0.692 ± 0.087, 0.947 ± 0.089, 0.38 ± 0.016 and 0.742 ± 0.042 µM, while nine scaffolds such as 1, 4, 6, 8, 9, 12, 13, 14 and 19 showed superior BuChE potency than standard drug having IC50 values 2.54 ± 0.10, 1.79 ± 0.20, 3.25 ± 0.18, 2.48 ± 0.05, 1.33 ± 0.05, 2.19 ± 0.08, 2.81 ± 0.20, 2.23 ± 0.10 and 2.10 ± 0.05 µM respectively. Nonetheless, remaining analogs were found to have moderate activity. Among the synthesized series, analogs 12 (IC50 = 0.38 ± 0.016 µM) and 9 (IC50 = 1.33 ± 0.05 µM) were identified as the most potent inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes. In addition, the molecular docking studies were carried out to find out the possible binding mode of interactions of most active analogs with enzymes active site and results supported the experimental data.