Thieno-Thiazolostilbenes, Thienobenzo-Thiazoles, and Naphtho-Oxazoles: Computational Study and Cholinesterase Inhibitory Activity

Abstract

Naphtho-triazoles and thienobenzo-triazoles have so far proven to be very potent inhibitors of the enzyme butyrylcholinesterase (BChE). Based on these results, in this work, new thienobenzo-thiazoles were designed and synthesized, and their potential inhibitory activity was tested and compared with their analogs, naphtho-oxazoles. The synthesis was carried out by photochemical cyclization of thieno-thiazolostilbenes obtained in the first reaction step. Several thienobenzo-thiazoles and naphtho-oxazoles have shown significant potential as BChE inhibitors, together with the phenolic thiazolostilbene being the most active of all tested compounds. These results are significant as BChE has been attracting growing attention due to its positive role in the treatment of Alzheimer’s disease. Computational examination based on the DFT approach enabled the characterization of the geometry and electronic structure of the studied molecules. Furthermore, the molecular docking study, accompanied by additional optimization of complexes ligand-active site, offered insight into the structure and stabilizing interactions in the complexes of studied molecules and BChE.

Cholinesterase Inhibition and Antioxidative Capacity of New Heteroaromatic Resveratrol Analogs: Synthesis and Physico-Chemical Properties

“…At the same time, the activity of BChE increases significantly (by 40 to 120% of the usual value). In the last few years, we have been designing and developing new potential cholinesterase inhibitors [36][37][38][39][40][41][42][43][44][45]. The synthesis was mainly performed by Wittig reaction, photochemical electrocyclization, and triazole ring alkylation, where all three stages were very favorable with high yields.…”