In Silico Study of Sesquiterpene and Monoterpene Compounds from Valerian Roots (Valerian officinalis) As Acetylcholinesterase Inhibitor

Abstract

Introduction: Alzheimer's is a central nervous system disease that can be treated with an acetylcholinesterase enzyme inhibitor drug (AChE), namely rivastigmine. Rivastigmine has side effects such as nausea, vomiting, loss of appetite, headache, weakness, and malaise. Alternative to deal with these side effects is an extracted compound from valerian root with bioactivity as an anti-dementia. The test compounds that performed the activity were 4 variations of sesquiterpenoids (volvalerenal H, volvalerenal I, volvalerenal J, volvalerenic acid K) and 1 monoterpenoid (densispicnins C). Objective: This study aimed to determine the molecular interaction of sesquiterpene and monoterpene compounds and pharmacokinetic of the best compound from molecular docking. Methods: This study was conducted with the stages of molecular docking simulation, prediction of pharmacokinetics and toxicity of compounds, and Lipinski’s Rule of Five parameters. Result: Volvalerenal J was the best compound from molecular docking simulation with a Gibbs free energy value of -7,48 kcal/mol, an inhibition constant of 1,30 μM, and interactions with amino acid residues His447 and Ser203. The values of HIA and CaCo2 were 100% and 46,76%, with the values of PPB and BBB were 96,57% and 0,88%. Respectively, volvalerenal J is not mutated but a carcinogen and fulfills the rules of Lipinski. Conclusion: Compound volvalerenal J has the highest potential to be the best acetylcholinesterase (AChE) inhibitor among other compounds in the extract valerian root.

Keywords: AChE, Valerian Root, Alzheimer's,  In silico