Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
Eur J Med Chem. 2011 Oct;46(10):4915-23. doi: 10.1016/j.ejmech.2011.07.048. Epub 2011 Aug 4.
Sixteen (1-16) dihydro-β-agarofuran sesquiterpenes were isolated from the fruits of Maytenus jelskii and evaluated against mammalian cells with a multidrug resistance phenotype mediated by the overexpression of the human P-glycoprotein. Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, CD studies, chemical correlations and biogenetic means. Eight compounds from this series were discovered as potent chemosensitizers (1, 2, 4, 6, 8, 9, 11 and 14), showing similar effectiveness to or higher than the classical P-glycoprotein reversal agent verapamil, a first-generation chemosensitizer, when reversing resistance to daunomycin and vinblastine. Detailed structure-activity relationships revealed that aromatic substituents at the 6 and 9-position of the sesquiterpene scaffold were able to modulate the intensity of inhibition.
从卫矛科美登木属植物密穗美登木果实中分离得到 16 个 1-16 去氢-β-大呋喃半萜，并对其进行了哺乳动物细胞活性评价。这些化合物对由人 P-糖蛋白过度表达介导的多药耐药表型具有抑制活性。根据光谱分析，包括 1D 和 2D NMR 技术、CD 研究、化学相关和生物发生手段，对其立体结构进行了阐明。该系列中的 8 个化合物被发现具有很强的化学增敏作用（1、2、4、6、8、9、11 和 14），在逆转柔红霉素和长春碱的耐药性方面，与经典的 P-糖蛋白逆转剂维拉帕米（第一代化学增敏剂）具有相似的效果或更高的效果。详细的结构-活性关系表明，在倍半萜骨架的 6 和 9 位的芳基取代基能够调节抑制强度。
