Su Bao-Ning, Jones William P, Cuendet Muriel, Kardono Leonardus B S, Ismail Rachman, Riswan Soedarsono, Fong Harry H S, Farnsworth Norman R, Pezzuto John M, Kinghorn A Douglas
Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Phytochemistry. 2004 Nov;65(21):2861-6. doi: 10.1016/j.phytochem.2004.08.007.
As part of our program directed towards the discovery of new cancer chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M. pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay-directed fractionation of this extract led to the isolation of two dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1) and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4-hydroxybenzaldehyde, and beta-sitosterol glucoside. The structures of compounds 1 and 2 were determined using spectroscopic data (1D and 2D NMR, and HREIMS), and the 8R and 8'R absolute stereochemistry was established for both 1 and 2 on the basis of their CD spectra. All isolates obtained in the present study were evaluated for their inhibitory effects with both COX-1 and -2. Of these, only 5'-methoxyyatein (3) showed weak activity against COX-2, while all other compounds isolated were inactive. The COX-2 inhibitory activity of the EtOAc extract was also traced to the presence of several common fatty acids by LC-MS.
作为我们从植物中发现新型癌症化学预防剂项目的一部分，人们发现苹果桑茎的乙酸乙酯可溶提取物能够抑制环氧合酶-2（COX-2）。对该提取物进行生物活性导向的分级分离，得到了两种二苄基丁内酯木脂素，即(8R,8'R)-3'-O-去甲基-5-羟基罗汉松脂素（1）和(8R,8'R)-3'-O-去甲基-5-甲氧基罗汉松脂素（2），以及七种已知化合物，(-)-5'-甲氧基水飞蓟宾（3）、二氢猕猴桃内酯A、(-)-脱氧鬼臼毒素（炭疽菌素）、(-)-脱氧足叶草酮、2,6-二甲氧基对苯二酚、4-羟基苯甲醛和β-谷甾醇葡萄糖苷。利用光谱数据（一维和二维核磁共振以及高分辨电子轰击质谱）确定了化合物1和2的结构，并根据它们的圆二色光谱确定了1和2的8R和8'R绝对立体化学构型。对本研究中获得的所有分离物进行了COX-1和COX-2抑制作用评估。其中，只有5'-甲氧基水飞蓟宾（3）对COX-2表现出微弱活性，而分离得到的所有其他化合物均无活性。通过液相色谱-质谱联用还发现，乙酸乙酯提取物的COX-2抑制活性也归因于几种常见脂肪酸的存在。
