Ibogan, Tacaman, and Cytotoxic Bisindole Alkaloids from Tabernaemontana. Cononusine, an Iboga Alkaloid with Unusual Incorporation of a Pyrrolidone Moiety
Ibogan, Tacaman, and Cytotoxic Bisindole Alkaloids from Tabernaemontana. Cononusine, an Iboga Alkaloid with Unusual Incorporation of a Pyrrolidone Moiety
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DOI：
10.1021/acs.jnatprod.5b00117
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发表时间：
2015-05-01
影响因子：
5.1
通讯作者：
Kam, Toh-Seok
中科院分区：
文献类型：
--
作者：
Lim, Kuan-Hon;Raja, Vijay J.;Kam, Toh-Seok
6种新的吲哚类生物碱，即康氏碱（1，一种罕见的伊波加-吡咯烷酮缀合物）、戊valueine(2)、长春麻碱(3)、他卡莫尼定(4)、6-氧伊波加碱(5)和n -4氯甲基去氟氯化木碱(6)，以及两种新的沃巴辛基-伊波加双吲哚类生物碱，ervatensines a(7)和B(8)，以及其他已知的生物碱，从马来亚Tabernaemontana corymbosa的茎皮提取物中分离得到。这些生物碱的结构是在核磁共振和质谱分析的基础上建立的，其中一个(7)是通过x射线衍射分析证实的。长春长春素(3)在逆转长春新碱耐药KB细胞的多药耐药方面表现出明显的活性（IC50为2.62 μ M），而ervatensines A(7)和B(8)以及另外两种已知的双吲哚对人KB细胞的体外生长抑制活性（IC50 < 2 μ M）。化合物7和8对A549、MCF-7、MDA-468、HCT-116和HT-29细胞也表现出良好的生长抑制活性（IC50为0.70 ~ 4.19 μ M）。细胞周期和膜联蛋白V-FITC凋亡实验表明，化合物7和8抑制HCT-116和MDA-468细胞的增殖，引起凋亡和坏死细胞死亡。
Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga-pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N-4-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 mu M), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 mu M). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70-4.19 mu M). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death.