Synthesis and molecular modelling of thiadizole based hydrazone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitory activities

ABSTRACT

Some novel substituted thiazolylhydrazine derivatives were designed, synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes and antioxidant activities were investigated. The structures of the synthesized compounds were determined using different spectroscopic techniques such as ¹H-NMR, ¹³C-NMR, and HRMS. According to the enzyme inhibition results, the synthesized compounds showed selectivity against BuChE enzyme inhibition. Compounds 5e, 5g, 5i and 5j displayed significant BuChE inhibition potencies. Among them, compound 5i was found to be the most effective derivative with an IC₅₀ value of 56.01 ± 0.054 µM. In addition, their antioxidant properties were evaluated in vitro through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. For compounds 5e, 5g, 5i and 5j in silico molecular docking and 100 ns molecular dynamics simulations studies against the BuChE enzyme were performed to determine possible protein-ligand interactions and stability. DFT-D3 study was performed to stabilize of compounds 5e, 5g, 5i and 5j both in gas and solvent medium and investigated their electronic properties. Of all geometries, that of DMSO is the lowest one.

KEYWORDS:

• Alzheimer’s disease
• antioxidant activity
• molecular docking
• thiazolylhydrazine
• DFT-D3

Acknowledgements

The numerical calculations reported in this paper were partially performed at Tubitak Ulakbim, High Performance and Grid Computing Center (TRUBA resources). Special thanks to WEBGRO Macromolecular Simulations (https://simlab.uams.edu/index.php) providing high-performance computing for their molecular dynamics simulations.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplemental data

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2022.2041723.

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Funding

The author(s) reported that there is no funding associated with the work featured in this article.