Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells
Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells
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DOI：
10.1021/jm9700169
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发表时间：
1997-06-20
影响因子：
7.3
通讯作者：
McLaughlin, JL
中科院分区：
文献类型：
--
作者：
Oberlies, NH;Chang, CJ;McLaughlin, JL
测试了十四种结构不同的番荔枝内酯，代表三种主要类型的双相邻、双非相邻和单-THF环，它们抑制阿霉素抗性人乳腺癌（MCF-7/Adr）细胞生长的能力。该细胞系对阿霉素、长春新碱和长春碱的治疗具有抗性，因此是多药耐药（MDR）的。在一系列双相邻THF环乙酸配基中，立体化学为苏式-反式-苏式-反式-双式（C-15至C-24）的那些乙酸配基是最有效的，其效力高达阿霉素的250倍。THF环系统的侧翼羟基和γ-不饱和内酯之间的13个碳的间距似乎是最佳的，其中11和9个碳的间距明显较不活跃。几种单-THF环化合物也相当有效，其中阿替曲辛A（11）是测试的最有效的化合物。因此，乙酸配基可能具有化学治疗潜力，特别是对于MDR肿瘤。
Fourteen structurally diverse Annonaceous acetogenins, representing the three main classes of bis-adjacent, bis-nonadjacent, and singie-THF ring(s), were tested for their ability to inhibit the growth of adriamycin resistant human mammary adenocarcinoma (MCF-7/Adr) cells. This cell line is resistant to treatment with adriamycin, vincristine, and vinblastine and is, thus, multidrug resistant (MDR), Among a series of bis-adjacent THF ring acetogenins, those with the stereochemistry of threo-trans-threo-trans-erythro (from C-15 to C-24) were the most potent with as much as 250 times the potency of adriamycin. A spacing of 13 carbons between the flanking hydroxyl of the THF ring system and the gamma-unsaturated lactone seems to be optimum with a spacing of 11 and 9 carbons being significantly less active. Several single-THF ring compounds, were also quite potent with gigantetrocin A (11) being the most potent compound tested. The acetogenins may, thus, have chemotherapeutic potential, especially with regard to MDR tumors.