In Vitro and In Silico Anti-Acetylcholinesterase Activity from Macaranga tanarius and Syzygium jambos

Macaranga tanarius (MT) and Syzygium jambos (SJ) are pharmacologically reported to have anti-oxidant, anti-inflammatory, and anti-diabetic effects, and can be neuroprotective agents. Our previous work revealed that MT and SJ exhibited 76.32% and 93.81% inhibition against acetylcholinesterase (AChE) at 50 μg/mL final concentration in their ethyl acetate and hexane fractions, respectively. This study was aimed to investigate the bioactive constituents of MT and SJ and their molecular mechanism toward AChE inhibition. Bioassay-guided isolation afforded prenylflavonoids 1–3 from MT and anacardic acid derivatives 4 and 5 from SJ that were confirmed by NMR and MS data. Compound 5 exerted the strongest anti-AChE potential (IC(50): 0.54 μM), followed by 1, 4, 3, and 2 (IC(50): 1.0, 2.4, 6.8, and 33 μM, respectively). In silico molecular docking revealed 5 formed stronger molecular interactions including three H-bonds than its derivative 4 based on the saturation of their alkyl chains. The addition of a five carbon-prenyl chain in 1 increased the number of binding interactions, justifying its greater activity than derivatives 2 and 3. This research reflects the first report of AChE inhibitors from these species, thereby adding pharmacological values to MT and SJ as potential remedies in neuroprotection.