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

Abstract A new unusual C-methylated chalcone was successfully isolated from the leaves of Syzygium dyerianum (King) Chantaran. & J.Parn, identified as syzydyerin A ( 1 ), together with β -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 1 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 1 exhibits strong binding affinities toward AChE (−11.0 kcal/mol) and 5-LOX (−9.1 kcal/mol), comparable to standard inhibitors, with key π – π stacking and hydrogen bonding interactions stabilizing its binding at both active sites, highlighting its promising dual inhibitory potential. The study underscores the value of S. dyerianum as a source of bioactive compounds with potential applications in treating neuroinflammatory diseases.