Cholinesterase Inhibitors from an Endophytic Fungus Aspergillus niveus Fv-er401: Metabolomics, Isolation and Molecular Docking

Abstract

Alzheimer’s disease poses a global health concern with unmet demand requiring creative approaches to discover new medications. In this study, we investigated the chemical composition and the anticholinesterase activity of Aspergillus niveus Fv-er401 isolated from Foeniculum vulgare (Apiaceae) roots. Fifty-eight metabolites were identified using UHPLC-MS/MS analysis of the crude extract. The fungal extract showed acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory effects with IC50 53.44 ± 1.57 and 48.46 ± 0.41 µg/mL, respectively. Two known metabolites were isolated, terrequinone A and citrinin, showing moderate AChE and BuChE inhibitory activity using the Ellman’s method (IC50 = 11.10 ± 0.38 µg/mL and 5.06 ± 0.15 µg/mL, respectively for AChE, and IC50 15.63 ± 1.27 µg/mL and 8.02 ± 0.08 µg/mL, respectively for BuChE). As evidenced by molecular docking, the isolated compounds and other structurally related metabolites identified by molecular networking had the required structural features for AChE and BuChE inhibition. Where varioxiranol G (−9.76 and −10.36 kcal/mol), penicitrinol B (−9.50 and −8.02 kcal/mol), dicitrinol A (−8.53 and −7.98 kcal/mol) and asterriquinone CT5 (−8.02 and −8.25 kcal/mol) showed better binding scores as AChE and BuChE inhibitors than the co-crystallized inhibitor (between −7.89 and 7.82 kcal/mol) making them promising candidates for the development of new drugs to treat Alzheimer’s.

Antioxidant and anticholinesterase properties of Echinometra mathaei and Ophiocoma erinaceus venoms from the Persian Gulf

“…The potent in vitro anti-AChE activity of indole alkaloid harmine ( S 5 ), as a harmala alkaloid (IC 50 : 9.05 μM), was reported by He et al ( He et al, 2015 ) that is confirmed the results obtained in the present in silico study. G 6 , also referred to as citrinin, exhibits moderate inhibitory activity against AChE and BuChE, as determined by the Ellman’s method (with an IC 50 value of 5.06 ± 0.15 μg/mL for AChE and 8.02 ± 0.08 μg/mL for BChE) ( Hamed et al, 2023 ).…”

Taming Food–Drug Interaction Risk: Potential Inhibitory Effects of Citrus Juices on Cytochrome Liver Enzymes Can Safeguard the Liver from Overdose Paracetamol-Induced Hepatotoxicity

“…UHPLC was run on an Agilent LC-MS system composed of an Agilent 1290 Infinity II UHPLC coupled to an Agilent 6545 ESI-Q-TOF-MS in both negative and positive modes. Aliquots (1 μL) of citrus juices (1 mg/mL in MeOH) were analyzed following the method previously described …”

“…Aliquots (1 μL) of citrus juices (1 mg/mL in MeOH) were analyzed following the method previously described. 73 5.5. Chemometric Analysis (Metabolic Discrimination of Citrus Fruits Using LC/MS Analyses Coupled with Chemometrics).…”

Identification of Antimicrobial Metabolites from the Egyptian Soil-Derived Amycolatopsis keratiniphila Revealed by Untargeted Metabolomics and Molecular Docking

“…Ultra-high performance liquid chromatographic (UHPLC) analysis was performed using an Agilent LC-MS system composed of an Agilent 1290 Infinity II UHPLC linked to an Agilent 6545 ESI-Q-TOF-MS according to the method described by Hamed et al [ 26 ], aliquots (1 µL) of EtOAc extract (1 mg/mL in MeOH) were assessed using a Kinetex phenyl-hexyl (1.7 μm, 2.1 × 50 mm) column. With a flow rate of 0.4 mL/min, the column was eluted with 1 min isocratic elution of 90% A (A: 100% water (H 2 O) + 0.1% formic acid) followed by 6 min linear gradient elution to 100% B (95% Acetonitrile (MeCN) + 5% H 2 O + 0.1% formic acid).…”