Abstract：
A four-step synthetic process has been developed to prepare 1,3,5,8-tetrahydroxyxanthone (2a) and its isomer 1,3,7,8-tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α-glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 μM and 63.2 ± 0.6 nM, respectively, which was far active than acarbose (35.0 ± 0.1 μM), and a little more active than epalrestat (67.0 ± 3.0 nM). 2a was also confirmed as the most active antioxidant in vitro with EC50 value of 8.9 ± 0.1 μM. Any structural modification including methylation, deletion, and position change of hydroxyl group in 2a will cause an activity loss in inhibitory and antioxidation. By applying a H2 O2 -induced oxidative stress nematode model, it was confirmed that xanthone 2a can be absorbed by Caenorhabditis elegans and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. 2a was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone 2a behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications.
摘要：
已开发出一种四步合成方法来制备1,3,5,8-四羟基黄吨酮（2a）及其异构体1,3,7,8-四羟基黄吨酮（2b）。通过改进的方案还合成了25个黄吨酮。黄原酮2a被认为是对α-葡萄糖苷酶和醛糖还原酶（ALR2）最具活性的抑制剂，IC50值为7.8±0.5μM和63.2±0.6nM，分别,远比阿卡波糖（35.0±0.1μM）活跃，并且比依帕司他（67.0±3.0nM）更活跃。2a也被证实为体外最具活性的抗氧化剂,EC50值为8.9±0.1μM。任何结构修饰，包括甲基化，删除,2a中羟基的位置改变会导致抑制和抗氧化活性丧失。通过应用H2O2诱导的氧化应激线虫模型，已证实，黄原酮2a可以被秀丽隐杆线虫吸收，并且可以生物利用来减弱体内氧化应激，包括对寿命的影响，超氧化物歧化酶,过氧化氢酶,还有丙二醛.2a具有体内降血糖作用和减轻高糖下胚胎畸形的作用。我们所有的数据都支持黄原酮2a具有三重作用，是治疗糖尿病的潜在药物，妊娠期糖尿病,和糖尿病并发症。
