Grupo Químico de Investigación y Desarrollo Ambiental, Programa de Licenciatura en Ciencias, Facultad de Educación, Universidad Surcolombiana , Neiva, Colombia.
Laboratorio de Genómica, Unidad de Investigación Básica, Instituto Nacional de Cancerología , 14080, Mexico City, Mexico.
J Nat Prod. 2016 Dec 23;79(12):3093-3104. doi: 10.1021/acs.jnatprod.6b00782. Epub 2016 Nov 23.
Multidrug resistance is the expression of one or more efflux pumps, such as P-glycoprotein, and is a major obstacle in cancer therapy. The use of new potent and noncytotoxic efflux pump modulators, coadministered with antineoplastic agents, is an alternative approach for increasing the success rate of therapy regimes with different drug combinations. This report describes the isolation and structure elucidation of six new resin glycosides from moon vine seeds (Ipomoea alba) as potential mammalian multidrug-resistance-modifying agents. Albinosides IV-IX (1-6), along with the known albinosides I-III (7-9), were purified from the CHCl-soluble extract. Degradative chemical reactions in combination with NMR spectroscopy and mass spectrometry were used for their structural elucidation. Four new glycosidic acids, albinosinic acids D-G (10-13), were released by saponification of natural products 3-6. They were characterized as tetrasaccharides of either convolvulinolic (11S-hydroxytetradecanoic) or jalapinolic (11S-hydroxyhexadecanoic) acids. The potentiation of vinblastine susceptibility in multidrug-resistant human breast carcinoma cells of albinosides 1-6 was evaluated by modulation assays. The noncytotoxic albinosides VII (4) and VIII (5), at a concentration of 25 μg/mL, exerted the strongest potentiation of vinblastine susceptibility, with a reversal factor (RF) of 201- and >2517-fold, respectively.
多药耐药性是一种或多种外排泵的表达，如 P-糖蛋白，是癌症治疗的主要障碍。使用新的有效且非细胞毒性的外排泵调节剂，与抗肿瘤药物联合使用，是增加不同药物组合治疗方案成功率的一种替代方法。本报告描述了从月光藤种子（Ipomoea alba）中分离和结构阐明六种新的树脂糖苷作为潜在的哺乳动物多药耐药性修饰剂。Albinosides IV-IX（1-6）与已知的 albinosides I-III（7-9）一起，从 CHCl 可溶提取物中纯化。降解化学反应结合 NMR 光谱和质谱用于其结构阐明。通过天然产物 3-6 的皂化释放出四个新的糖苷酸，albinosinic 酸 D-G（10-13）。它们被表征为 either convolvulinolic（11S-hydroxytetradecanoic）或 jalapinolic（11S-hydroxyhexadecanoic）酸的四糖。通过调制测定评估 albinosides 1-6 在多药耐药性人乳腺癌细胞中对长春碱敏感性的增强作用。非细胞毒性的 albinosides VII（4）和 VIII（5）在 25μg/mL 浓度下，对长春碱敏感性的增强作用最强，逆转因子（RF）分别为 201 倍和>2517 倍。
