Abdullah Nor Hayati, Thomas Noel Francis, Sivasothy Yasodha, Lee Vannajan Sanghiran, Liew Sook Yee, Noorbatcha Ibrahim Ali, Awang Khalijah
Natural Product Division, Forest Research Institute Malaysia, 52109 Kepong, Malaysia.
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Int J Mol Sci. 2016 Feb 14;17(2):143. doi: 10.3390/ijms17020143.
The mammalian hyaluronidase degrades hyaluronic acid by the cleavage of the β-1,4-glycosidic bond furnishing a tetrasaccharide molecule as the main product which is a highly angiogenic and potent inducer of inflammatory cytokines. Ursolic acid 1, isolated from Prismatomeris tetrandra, was identified as having the potential to develop inhibitors of hyaluronidase. A series of ursolic acid analogues were either synthesized via structure modification of ursolic acid 1 or commercially obtained. The evaluation of the inhibitory activity of these compounds on the hyaluronidase enzyme was conducted. Several structural, topological and quantum chemical descriptors for these compounds were calculated using semi empirical quantum chemical methods. A quantitative structure activity relationship study (QSAR) was performed to correlate these descriptors with the hyaluronidase inhibitory activity. The statistical characteristics provided by the best multi linear model (BML) (R² = 0.9717, R²cv = 0.9506) indicated satisfactory stability and predictive ability of the developed model. The in silico molecular docking study which was used to determine the binding interactions revealed that the ursolic acid analog 22 had a strong affinity towards human hyaluronidase.
哺乳动物透明质酸酶通过切割β-1,4-糖苷键降解透明质酸，产生四糖分子作为主要产物，该四糖分子是一种高度促血管生成且强力诱导炎性细胞因子的物质。从四角棱柱草中分离得到的熊果酸1被鉴定具有开发透明质酸酶抑制剂的潜力。一系列熊果酸类似物要么通过对熊果酸1进行结构修饰合成，要么从商业途径获得。对这些化合物对透明质酸酶的抑制活性进行了评估。使用半经验量子化学方法计算了这些化合物的几个结构、拓扑和量子化学描述符。进行了定量构效关系研究（QSAR），以将这些描述符与透明质酸酶抑制活性相关联。最佳多元线性模型（BML）（R² = 0.9717，R²cv = 0.9506）提供的统计特征表明所开发模型具有令人满意的稳定性和预测能力。用于确定结合相互作用的计算机模拟分子对接研究表明，熊果酸类似物22对人透明质酸酶具有很强的亲和力。
