School of Biosciences, Taylor's University, Lakeside Campus, Subang Jaya, Malaysia.
School of Chemical Sciences, Universiti Sains Malaysia, George Town, Malaysia.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):627-639. doi: 10.1080/14756366.2021.1882452.
A new series of 3--substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (, , , , , -, -) exhibited significant effects with the IC values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9-xanthen-9-one () and ethyl 2-((9-oxo-9-xanthen-3-yl)oxy)acetate () showed a mixed inhibition mechanism. Molecular docking study showed that binds to the active site of AChE and interacts via extensive π-π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π-π interaction with the phenol side chain of Y72. This study revealed that 3--alkoxyl substituted xanthone derivatives are potential lead structures, especially and which can be further developed into potent AChE inhibitors.
一系列新的 3-取代黄烷酮衍生物被合成并评估了它们对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的抗胆碱能活性。结果表明，黄烷酮衍生物具有良好的 AChE 抑制活性，其中 11 种（、、、、、、-、-）具有显著的效果，IC 值范围为 0.88 至 1.28 μM。3-(4-苯基丁氧基)-9-黄烷酮（）和乙酯 2-((9-氧代-9-黄烷-3-基）氧基）乙酸酯（）的 AChE 酶动力学研究表明其为混合抑制机制。分子对接研究表明，与 AChE 的活性位点结合，并通过与 Trp86 和 Tyr337 的吲哚和酚侧链的广泛 π-π 堆积相互作用，以及与水合位点的氢键和与 Y72 的酚侧链的 π-π 相互作用。这项研究表明，3--烷氧基取代的黄烷酮衍生物是潜在的先导结构，特别是和，它们可以进一步开发为有效的 AChE 抑制剂。
