Syzydyerin A, a new unusual C-methylated chalcone isolated from the leaves of <i>Syzygium dyerianum</i> (King) Chantar. &amp; J.Parn

A new unusual C-methylated chalcone was successfully isolated from the leaves of <i>Syzygium dyerianum</i> (King) Chantaran. & J.Parn, identified as syzydyerin A (<b>1</b>), together with <i>β</i>-sitosterol, friedelin and lupeol. The characterisation and structural elucidation of the isolated compounds were established by extensive spectroscopic data analysis and comparison with literature data. Compound <b>1</b> exhibited inhibitory activity against acetylcholinesterase (AChE) and lipoxygenase (LOX) with IC50 values of 50.4 ± 0.2 µm and 30.7 ± 0.25 µm, respectively, compared to the reference inhibitors galantamine (IC50 = 40.7 ± 0.12 µm) for AChE and quercetin (IC50 = 3.5 ± 0.13 µm) 5-LOX. Molecular docking analysis revealed that compound <b>1</b> exhibits strong binding affinities toward AChE (-11.0 kcal/mol) and 5-LOX (-9.1 kcal/mol), comparable to standard inhibitors, with key <i>π</i>-<i>π</i> stacking and hydrogen bonding interactions stabilizing its binding at both active sites, highlighting its promising dual inhibitory potential. The study underscores the value of <i>S. dyerianum</i> as a source of bioactive compounds with potential applications in treating neuroinflammatory diseases.