Sesquiterpenoids from the rhizomes of Homalomena pendula (Blume) Bakh.f showing acetylcholinesterase inhibitory activity: in vitro and in silico studies

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, leading to a slow and irreversible decline in mental function. Cholinergic impairment has been recognized as one of the reasons leading to cognitive degradation in this disease; therefore, the inhibitors of acetylcholinesterase (AChE) are current important therapeutic agents. This study aimed to evaluate the AChE inhibitory activities of sesquiterpenoids from the rhizomes of Homalomena pendula. Among fourteen isolates, teucmosin showed a significant AChE inhibition with an IC50 value of 4.53 +/- 0.39 mu M, which was comparable to berberine (positive control, IC50 =3.78 +/- 0.51 RM). The in silico investigations indicated that teucmosin possessed good pharmacokinetic properties, drug-likeness, and low toxicities on most common targets in AD. The molecular docking study and molecular dynamics simulation revealed the mode of interaction of teucmosin with the enzyme and indicated that this compound could serve as a dual binding site (CAS and PAS) inhibitor of AChE. Teucmosin could be considered as a promising candidate for AD due to its significant anti-cholinesterase activity. [GRAPHICS] .