Abstract
The purpose of this study was to investigate essential oils content, phytochemicals, computational modelling and bioactivities of four Knema species (Myristicaceae). Essential oils were extracted via hydrodistillation and were analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Phytochemicals were isolated using silica gel column chromatography and their chemical structures were elucidated via spectroscopic methods including nuclear magnetic resonance, infrared spectroscopy, mass spectrometry, and ultraviolet-visible spectroscopy. Computational studies were performed to assess the binding of isolated compounds to acetylcholinesterase (AChE) and 5-lipoxygenase (5-LOX), and their antibiofilm activities. The major components of the four Knema essential oils were as following: K. intermedia (_-muurolol, 20.1%), K. malayana (_-cadinene, 20.2%), K. hookeriana (_-caryophyllene, 26.2%), and K. furfuracea (bicyclogermacrene, 23.1%). Phytochemical investigation led to isolation of a new compound (intermedianin) from K. intermedia and 22 known compounds including five from K. intermedia (cubebin, cubebin acetate, bicubebin B, apigenin, and kaempferol), six from K. malayana (3_,4_,5,7-tetramethoxyflavone, 3_,4_,5_,5,7-pentamethoxyflavone, 4_-hydroxy-3_,5_,5,7- tetramethoxyflavone, 3-hydroxy-3_,4_,5_,5,7-pentamethoxyflavone, 3,3_,5_,5,7- pentamethoxyflavone, and stigmasterol), seven from K. hookeriana (aptosimon, cubebin acetate, bicubebin A, 5,7-dimethoxyflavone, 4_,5,7-trimethoxyflavone, luteolin, and epicatechin), and four from K. furfuracea (cubebin, cubebin acetate, bicubebin A, and stigmasterol). Molecular docking studies revealed that intermedianin and aptosimon strongly bind AChE (_11.7 and _12.0 kcal/mol). Aptosimon showed strong binding affinity to 5-LOX (_10.1 kcal/mol) and intermedianin displayed binding to fungal cytochrome enzyme (CYP51B) (_11.0 kcal/mol). Bioactivity studies showed that 3_,4_,5_,5,7-pentamethoxyflavone gave strongest AChE inhibition (IC50 10.2 _M), while bicubebin A was the most active against 5-LOX (IC50 15.9 _M), and intermedianin was the strongest inhibitor of Candida albicans biofilm (22.8%). In conclusion, the current study demonstrated that the essential oils and isolated compounds of the four Knema species exhibited strong AChE, 5-LOX, and fungal biofilm inhibitory activities. These findings suggest that the Knema species have potential as alternative treatments for brain disorders, inflammation, and fungal infections.