Antiradical and anti-acethylcholinesterase constituents from the methylene chloride extract of Ganoderma applanatum (Pers.) Pat (Ganodermataceae) and molecular docking study

Abstract

Alzheimer’s disease (AD) is a non-communicable disease with global impact. Inhibitors of acetylcholinesterase (AChE) are suitable therapies for AD. In this work, we report the isolation of antiacetylcholinesterase compounds from the methylene chloride (DCM) extract of the medical fungus Ganoderma applanatum (Pers.) Pat (Ganodermataceae). Chemical evaluation of this extract using chromatographic technics led to the isolation of a (1:1) mixture of ergosterol (1) and stellasterol (2), palmitic acid (3), ganodermanondiol (4), lucidumol B (5) and lupeol (6). Structures of these compounds were determined using spectroscopic analysis such as IR, MS, 1D & 2D NMR and literature. The acetylation reaction has been performed on the mixture (1 + 2) and compound 4, leading to the obtention the mixture of 3-acetyl-ergosterol (7) and 3-acetylstellasterol (8) along with 24-acetyl-ganodermanondiol (9) respectively. Total phenolic content was determined for DCM, Ethyl acetate and n-butanol extracts. To assess their antiradical scavenging potential, DPPH was used as free radical. The Inhibition power of acetylcholinesterase was evaluated in vitro using the Ellman reagent. Amongst all tested extracts, the DCM extract showed the high amount of total phenolic compounds with a value of 133.9512 mg EAG/g EX. The same extract showed a very good antiradical scavenging potential with an IC50 of 0.0021 mg/mL. The mixture (1 + 2) showed the highest antiradical scavenging activity with IC50 of 0.0770 mg/mL. The results obtained demonstrated that the acetylation has reduced the antiradical scavenging potential. Concerning the acetylcholinesterase inhibition power, the DCM extract and the mixture (1 + 2) showed a very good power with an inhibition percentage of 89%. The acetylation has also reduced the activity of the obtained derivative. The results provide insights into the potential efficacy of these compounds as acetylcholinesterase inhibitors. The binding interactions of the isolated and acetylated derivatives against acetylcholinesterase protein (PBP 3i6m) of Torpedo californica were studied using Autodock software. Ergosterol (−11.9 kcal/mol) binds better to the protein biding site through significant pi-sigma interactions.