Anti-AChE and Anti-BuChE Screening of the Fermentation Broth Extracts from Twelve Aspergillus Isolates and GC-MS and Molecular Docking Studies of the Most Active Extracts

Nowadays, the administration of cholinesterase enzyme (acetylcholinesterase: AChE and butyrylcholinesterase: BuChE) inhibitors is very common for the symptomatic treatment of Alzheimer's disease and the other forms of dementia and CNS disorders. In this paper, the anti-AChE and anti-BuChE activities of the fermentation broth ethyl acetate extracts from twelve Aspergillus isolates were evaluated by Ellman method. The results showed that A1 (Aspergillus flavus) and A5 (Aspergillus tubingensis, isolate 1) extracts with IC₅₀ values of 46.77 μg/mL and 75.85 μg/mL possess the greatest ability to inhibit AChE and BuChE, respectively. GC-MS analysis of the extracts (A1 and A5) demonstrated that two alkaloids named 14-methyl-16-azabicyclo[10.3.1]hexadeca-1(15),12(16),13-triene (MAHT) and 6-chloro-2-methyl-7,8,9,10-tetrahydro-phenanthridine (CMTP) account for the highest percentage of A1 (26.95%) and A5 (25.5%) extracts, respectively. A 2-pyrazoline derivative, 5-hydroxy-3-(4-pyridinyl)-5-trifluoromethyl-1-(2,4,6-trimethylphenoxyacetyl)- (PHPTT), also constituted the high percentage (9.54%) of A5 extract. The anticholinesterase and neuroprotective effects of some 2-pyrazoline derivatives have been previously reported. The interaction study of MAHT with human AChE and CMTP and PHPTT with human BuChE using molecular docking indicated that these alkaloids bind to the active site gorge of the enzymes with high affinity. The best docking scores of MAHT, CMTP, and PHPTT were -7.1, -8.2, and -9.7 kcal/mol, respectively.