Design, Synthesis, Biological Activity, and Molecular Modeling of Novel Spiroquinazoline Derivatives as Acetylcholinesterase Inhibitors for Alzheimer Disease

Abstract

The p-toluene sulfonic acid (p-TSA) catalyzed cascade ring closing transformation has been executed for the preparation of novel spiroquinazolinone compounds 4 and 5 by the reaction between anthranilamide and cyclohexanone followed by subsequent acylation. These molecules were then examined against the inhibitory activity of Acetylcholineterase (AchE). The tested compounds revealed moderate anti-AChE activity of IC₅₀ values ranging from 46.675 to 14.256 µM). The described results lead toward the development of compounds 4b and 5c having promising anti-AChE activities with IC₅₀ values at the micromolar level. The docking study suggests that these hybrid spiroquinazolinone scaffold might facilitate the further development of investigated compounds as anti-Alzheimer agents.

Keywords:

• Spiroquinazoline
• acetylcholinesterase inhibitors
• Alzheimer’s disease
• AchE
• IC50 values

Acknowledgments

We gratefully acknowledge the financial and research support from Chemistry Department, the Hashemite University. The authors are grateful to all the co-workers whose names appeared in the references. Also, we are grateful to the Middle East University, MEU, Jordan, for the academic license of the software’s used in this research article.

Disclosure statement

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

Additional information

Funding

This work was supported by Chemistry Department, the Hashemite University.