Mangosteen, Garcinia mangostana L., is known as the "Queen of fruits" and can be cultivated in the tropical rainforest such as Malaysia, Indonesia, and Thailand. Compounds isolated from the fruit peel of mangosteen contain abundant xanthones (especially alpha-mangostin). It has been used as traditional medicine such as anti-inflammatory and antibacterial and is popularly applied to cosmetic and pharmaceutical products. However, there is little information for quality and quantity determination of alpha-mangostin in mangosteen. Thus, the aim of this study was to set up a validated and stability-indicated isocratic reverse-phase high-performance liquid chromatographic (HPLC) method for quality control and quantity determination of a-mangostin from mangosteen peel extract. The assay was fully validated and shown to be linear (r(2) > 0.999), sensitive (LOD = 0.02 microg/mL and LOQ = 0.08 microg/mL), accurate (intra-day was between 98.1-100.8%, inter-day was between 90.0-101.3%), precise (intra-day variation < or = 1.8%, inter-day variation < or = 4.3%), specific, and with good recovery. Total analysis was approximately 8 min. The finalized method is also a stability-indicating assay. The present method should be useful for analytical research and for routine quality control analysis of alpha-mangostin in mangosteen peel extract and products of mangosteen.
Sixteen novel coumarin-based compounds are reported as potent acetylcholinesterase (AChE) inhibitors. The most active compound in this series, 5a (IC50 0.04 ± 0.01 µM), noncompetitively inhibited AChE with a higher potency than tacrine and galantamine. Compounds 5d, 5j, and 5 m showed a moderate antilipid peroxidation activity. The compounds showed cytotoxicity in the same range as the standard drugs in HEK-293 cells. Molecular docking demonstrated that 5a acted as a dual binding site inhibitor. The coumarin moiety occupied the peripheral anionic site and showed π-π interaction with Trp278. The tertiary amino group displayed significant cation-π interaction with Phe329. The aromatic group showed π-π interaction with Trp83 at the catalytic anionic site. The long chain of methylene lay along the gorge interacting with Phe330 via hydrophobic interaction. Molecular docking was applied to postulate the selectivity toward AChE of 5a in comparison with donepezil and tacrine. Structural insights into the selectivity of the coumarin derivatives toward huAChE were explored by molecular docking and 3D QSAR and molecular dynamics simulation for 20 ns. ADMET analysis suggested that the 2-(2-oxo-2H-chromen-4-yl)acetamides showed a good pharmacokinetic profile and no hepatotoxicity. These coumarin derivatives showed high potential for further development as anti-Alzheimer agents.