Abstract

Oleanolic acid (OA) is a natural cosmeceutical compound with various skin beneficial activities including inhibitory effect on hyaluronidase but the anti-hyaluronidase activity and mechanisms of action of its synthetic analogues remain unclear. Herein, a series of OA derivatives were synthesised and evaluated for their inhibitory effects on hyaluronidase. Compared to OA, an induction of fluorinated (6c) and chlorinated (6g) indole moieties led to enhanced anti-hyaluronidase activity (IC₅₀ = 80.3 vs. 9.97 and 9.57 µg/mL, respectively). Furthermore, spectroscopic and computational studies revealed that 6c and 6g can bind to hyaluronidase protein and alter its secondary structure leading to reduced enzyme activity. In addition, OA indole derivatives showed feasible skin permeability in a slightly acidic environment (pH = 6.5) and 6c exerted skin protective effect by reducing cellular reactive oxygen species in human skin keratinocytes. Findings from the current study support that OA indole derivatives are potential cosmeceuticals with anti-hyaluronidase activity.

摘要

齐墩果酸 (OA) 是一种天然药妆化合物，具有多种皮肤有益活性，包括对透明质酸酶的抑制作用，但其合成类似物的抗透明质酸酶活性和作用机制尚不清楚。在此，合成了一系列 OA 衍生物并评估了它们对透明质酸酶的抑制作用。与 OA 相比，氟化 ( 6c ) 和氯化 ( 6g ) 吲哚部分的诱导导致抗透明质酸酶活性增强（IC ₅₀ = 80.3，分别为 9.97 和 9.57 µg/mL）。此外，光谱和计算研究表明，6c和6g可以与透明质酸酶蛋白结合并改变其二级结构，导致酶活性降低。此外，OA吲哚衍生物在微酸性环境（pH = 6.5）中表现出可行的皮肤渗透性，6c通过减少人皮肤角质形成细胞中的细胞活性氧而发挥皮肤保护作用。当前研究的结果支持 OA 吲哚衍生物是具有抗透明质酸酶活性的潜在药妆品。