SW Center for Natural Products Research and Commercialization, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 E. Valencia Road, Tucson, Arizona 85706, United States.
J Nat Prod. 2012 Mar 23;75(3):361-9. doi: 10.1021/np200769q. Epub 2012 Jan 20.
Four new ent-kaurane diterpenoids, geopyxins A-D (1-4), were isolated from Geopyxis aff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxis sp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5 and 6), together with 1 and 3. The structures of 1-6 were established on the basis of their spectroscopic data, while the absolute configurations were assigned using modified Mosher's ester method. Methylation of 1-3, 5, and 6 gave their corresponding methyl esters 7-11. On acetylation, 1 and 7 yielded their corresponding monoacetates 12 and 14 and diacetates 13 and 15. All compounds were evaluated for their cytotoxic and heat-shock induction activities. Compounds 2, 7-10, 12, 14, and 15 showed cytotoxic activity in the low micromolar range against all five cancer cell lines tested, but only compounds 7-9, 14, and 15 were found to activate the heat-shock response at similar concentrations. From a preliminary structure-activity perspective, the electrophilic α,β-unsaturated ketone carbonyl motif present in all compounds except 6 and 11 was found to be necessary but not sufficient for both cytotoxicity and heat-shock activation.
从出现在 Pseudevernia intensa 地衣中的真菌 Geopyxis aff. majalis 中分离得到四个新的-ent-贝壳杉烷二萜，分别为 geopyxin A-D（1-4），而栖息在同一宿主上的 Geopyxis sp. AZ0066 则产生了两个新的-ent-贝壳杉烷二萜，分别为 geopyxin E 和 F（5 和 6），以及 1 和 3。基于其光谱数据确定了 1-6 的结构，而绝对构型则使用改进的 Mosher 酯法进行了分配。1-3、5 和 6 的甲基化得到了它们相应的甲酯 7-11。在乙酰化作用下，1 和 7 分别生成了它们相应的单乙酸酯 12 和 14 以及二乙酸酯 13 和 15。所有化合物都评估了其细胞毒性和热休克诱导活性。化合物 2、7-10、12、14 和 15 在低微摩尔范围内对所有五种测试的癌细胞系均显示出细胞毒性活性，但只有化合物 7-9、14 和 15 在相似浓度下被发现激活热休克反应。从初步的结构-活性角度来看，除了 6 和 11 之外，所有化合物中存在的亲电 α,β-不饱和酮羰基基序被发现对于细胞毒性和热休克激活是必要的，但不是充分的。
