To be ionized or not to be ionized: the vital role of physicochemical properties of galbanic acid derivatives in AChE assay

Abstract

Alzheimer’s disease is a progressive neurodegenerative disorder and patients suffer from memory loss, a decline in language skill and impairment in other cognitive functions. In the cholinergic hypothesis, dysfunction of cholinergic neurons especially in the hippocampus and cerebral cortex contributes to cognitive decline in patients. So agents that enhance acetylcholine concentration could improve cognitive function. AChEIs are among the most studied anti-Alzheimer agents. Galbanic acid as a natural compound with a sesquiterpene coumarin scaffold is a weak inhibitor of AChE. In the present contribution, we discussed the impact of carboxylic group ionization on inhibitory effects. We performed in vitro and in silico studies on galbanic acid, methyl and ethyl galbanates as AChE inhibitors. The order of inhibitory effect on AChE was obtained as ethyl galbanate ∼ methyl galbanate > galbanic acid. Our study highlights the important role of the physicochemical properties of natural lead compounds in each specific assay.

Communicated by Ramaswamy H. Sarma

Keywords:

• Alzheimer’s disease
• AChE
• galbanic acid derivatives
• sesquiterpene coumarin
• Ferula pseudalliacea
• molecular modeling

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

We are grateful to Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences (No. 950117130) for financial support of this work.