Muñoz-Martínez Francisco, Mendoza Cristina R, Bazzocchi Isabel L, Castanys Santiago, Jiménez Ignacio A, Gamarro Francisco
Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18100 Armilla, Granada, Spain.
J Med Chem. 2005 Jun 30;48(13):4266-75. doi: 10.1021/jm058003f.
In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation and biological activity of fourteen new and five known dihydro-beta-agarofuran sesquiterpenes from the leaves of Zinowiewia costaricensis (1-19). Their structures were determined by means of (1)H and (13)C NMR spectroscopic studies, including homonuclear and heteronuclear correlation experiments. The absolute configurations of the new compounds were determined by CD studies, chemical correlations or biogenetic grounds. All the natural compounds and derivative 20 have been tested on human MDR1-transfected NIH-3T3 cells, to determine their ability to revert the multidrug resistance phenotype due to P-glycoprotein overexpression. Six compounds from this series (1, 8, 11, 12, 13 and 14) showed similar effectiveness to the classical P-glycoprotein modulator verapamil when reversing resistance to daunorubicin, but it is up to sixteen times greater than that of verapamil when reversing resistance to vinblastine. The structure-activity relationships are discussed.
在一项对南美药用植物的深入研究中，我们在此报告了从哥斯达黎加齐诺维耶维亚（Zinowiewia costaricensis）叶子中分离出的14种新的和5种已知的二氢-β-agarofuran倍半萜的分离、结构解析及生物活性（1 - 19）。它们的结构通过（1）H和（13）C NMR光谱研究确定，包括同核和异核相关实验。新化合物的绝对构型通过圆二色性（CD）研究、化学关联或生源依据来确定。所有天然化合物及衍生物20已在转染了人MDR1的NIH - 3T3细胞上进行测试，以确定它们逆转因P - 糖蛋白过表达导致的多药耐药表型的能力。该系列中的6种化合物（1、8、11、12、13和14）在逆转对柔红霉素的耐药性时显示出与经典P - 糖蛋白调节剂维拉帕米相似的效果，但在逆转对长春碱的耐药性时，其效果比维拉帕米高16倍。文中讨论了构效关系。
