Bai Yan, Yi Ping, Zhang Songya, Hu Jiangchun, Pan Huaqi
Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, China.
The Key Laboratory of Chemistry for Natural Product of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
J Fungi (Basel). 2021 Oct 27;7(11):913. doi: 10.3390/jof7110913.
Oxidative stress plays a very important role in the progression of diabetes and its complications. A therapeutic agent that is both antidiabetic and antioxidant would be the preferred choice for the treatment of diabetes. The crude extract of the endophytic fungus F4a has significant antioxidant and -glycosidase and protein tyrosine phosphatase 1B (PTP1B) inhibition activities. Chemical investigation of F4a using an activity-guided isolation led to the discovery of three new compounds called peniorcinols A-C (-) along with six known compounds: penialidins A (), penialidin F (), myxotrichin C (), riboflavin (), indole-3-acetic acid (), and 2-(4-hydroxy-2-methoxy-6-methylphenyl) acetic acid (). Their chemical structures were established by their NMR and HRESIMS. The absolute configurations of and were determined by experimental and calculated electronic circular dichroism (ECD). Their antioxidant activities were evaluated by DPPH and ABTS scavenging assays. Compounds - and - showed moderate to strong free radical scavenging activities. Significantly, - exhibited more potent ABTS scavenging activity than that of the positive control. Their -glycosidase and PTP1B inhibition activities were tested. Among them, compound showed α-glucosidase inhibition activity, and compounds and showed PTP1B inhibitory activity for the first time. It is worth noting that and displayed both antioxidant and -glycosidase or PTP1B inhibition activities. These finding suggest that compounds and could be used as lead compounds to generate new potent drugs for the treatment of oxidative stress-related diabetes.
氧化应激在糖尿病及其并发症的进展中起着非常重要的作用。一种兼具抗糖尿病和抗氧化作用的治疗剂将是治疗糖尿病的首选。内生真菌F4a的粗提物具有显著的抗氧化、α-糖苷酶和蛋白酪氨酸磷酸酶1B（PTP1B）抑制活性。采用活性导向分离法对F4a进行化学研究，发现了三种新化合物，即青霉醇A-C（-），以及六种已知化合物：青霉菌素A（）、青霉菌素F（）、黏液菌素C（）、核黄素（）、吲哚-3-乙酸（）和2-（4-羟基-2-甲氧基-6-甲基苯基）乙酸（）。通过核磁共振和高分辨电喷雾电离质谱确定了它们的化学结构。通过实验和计算电子圆二色光谱（ECD）确定了和的绝对构型。通过DPPH和ABTS自由基清除试验评估了它们的抗氧化活性。化合物-和-表现出中度至强的自由基清除活性。值得注意的是，-表现出比阳性对照更强的ABTS自由基清除活性。测试了它们对α-糖苷酶和PTP1B的抑制活性。其中，化合物表现出α-葡萄糖苷酶抑制活性，化合物和首次表现出PTP1B抑制活性。值得注意的是，和同时表现出抗氧化以及α-糖苷酶或PTP1B抑制活性。这些发现表明，化合物和可作为先导化合物，用于开发治疗氧化应激相关糖尿病的新型强效药物。
