Investigating the disease-modifying properties of sclerotiorin in Alzheimer's therapy using acetylcholinesterase inhibition.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder caused due to the damage and loss of neurons in specific brain regions. It is the most common form of dementia observed in older people. The symptoms start with memory loss and gradually cause the inability to speak and do day-to-day activities. The cost of caring for those affected individuals is huge and is probably beyond most developing countries capability. Current pharmacotherapy for AD includes compounds that aim to increase neurotransmitters at nerve endings. This can be achieved by cholinergic neurotransmission through inhibition of the cholinesterase enzyme. The current research aims to find natural substances that can be used as drugs to treat AD. The present work identifies and explains compounds with considerable Acetylcholinesterase (AChE) inhibitory activities. The pigment was extracted from the Penicillium mallochii ARA1 (MT373688.1) strain using ethyl acetate, and the active compound was identified using chromatographic techniques followed by structural confirmation with NMR. AChE inhibition experiments, enzyme kinetics, and molecular dynamics simulation studies were done to explain the pharmacological and pharmacodynamic properties. We identified that the compound sclerotiorin in the pigment has AChE inhibitory activity. The compound is stable and can bind to the enzyme non-competitively. Sclerotiorin obeys all the drug-likeliness parameters and can be developed as a promising drug in treating AD.