Conolodinines A-D, Aspidosperma-Aspidosperma Bisindole Alkaloids with Antiproliferative Activity from Tabernaemontana corymbosa
Conolodinines A-D, Aspidosperma-Aspidosperma Bisindole Alkaloids with Antiproliferative Activity from Tabernaemontana corymbosa
复制标题
DOI：
10.1021/acs.jnatprod.8b00919
复制
发表时间：
2019-04-01
影响因子：
5.1
通讯作者：
Kam, Toh-Seok
中科院分区：
文献类型：
--
作者：
Sim, Dawn Su-Yin;Navanesan, Suerialoasan;Kam, Toh-Seok
对马来Tabernaemontana corymbosa叶的乙醇提取物进行了检查，结果分离出四种新的（1-4）和两种已知的Aspidosperma-Aspidosperma型双吲哚生物碱（5，6）。这些生物碱的结构是根据光谱数据（NMR和HRESIMS）的分析确定的。通过对相关的双吲哚生物碱conophylline（5）和conophyllinine（6）的X射线衍射分析，确定了它们的绝对构型。用苯硒酸酐处理双吲哚生物碱conophylline（5），除了以前从另一种马来Tabernaemontana中分离出的已知的双吲哚polyervinine（7）外，还得到另一种双吲哚产物8，一种可分离的7的互变异构体。X-射线衍射分析得到了两种双吲哚的绝对构型，此外还表明聚麦角碱（7）主要以中性二酮结构存在。双吲哚（1-8）和相关的茶碱型双吲哚（9-13）对一系列人癌细胞系，包括KB、长春新碱抗性KB、PC-3、LNCaP、MCF 7、MDA-MB-231、A549、HT-29和HCT 116细胞显示出明显的体外生长抑制活性，活性化合物的IC 50值在0.01-5 μ M范围内。
Examination of the EtOH extract of the leaves of the Malayan Tabernaemontana corymbosa resulted in the isolation of four new (1-4) and two known bisindole alkaloids (5, 6) of the Aspidosperma-Aspidosperma type. The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and HRESIMS). Xray diffraction analyses of the related bisindole alkaloids conophylline (5) and conophyllinine (6) established the absolute configurations. Treatment of the bisindole alkaloid conophylline (5) with benzeneselenic anhydride gave, in addition to the known bisindole polyervinine (7) previously isolated from another Malayan Tabernaemontana, another bisindole product, 8, an isolable tautomer of 7. X-ray diffraction analyses yielded the absolute configurations of both bisindoles and in addition showed that polyervinine (7) exists primarily as the neutral dione structure. The bisindoles (1-8) and the related conophylline-type bisindoles (9-13) showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, A549, HT-29, and HCT 116 cells, with IC50 values for the active compounds in the 0.01-5 mu M range.