82789-23-9Relevant articles and documents
Novel β-carboline-based indole-4,7-quinone derivatives as NAD(P)H: Quinone-oxidoreductase-1 inhibitor with potent antitumor activities by inducing reactive oxygen species, apoptosis, and DNA damage
Guo, Yibing,Xu, Liancheng,Ling, Changchun,Yang, Tao,Zheng, Wenjie,Lv, Jin,Guo, Qingsong,Chen, Bohua
, p. 1433 - 1446 (2020/07/13)
Eighteen new β-carboline-based indole-4,7-quinone derivatives (12a–i and 13a–i) were designed and synthesized, and their in vitro and in vivo antiproliferative activities were studied. Most of target compounds showed strong inhibition on three human tumor cells' proliferation. In particular, the most active compound 13g not only displayed more prominent antiproliferative activities than β-lapachone, a clinical antitumor candidate, but also exerted significant NAD(P)H: quinone-oxidoreductase-1 (NQO1) inhibitory activity and NQO1-dependent cytotoxicity in HT29 cells. Furthermore, 13g dose-dependently induced high ROS levels in HT29 cells, and selectively inhibited cancer cell but not non-tumor colon cell proliferation in vitro. Importantly, 13g promoted HT29 cell apoptosis and DNA damage by regulating relative apoptotic proteins and H2AX expression. Finally, 13g displayed significant growth inhibition of HT29 human colorectal adenocarcinoma xenograft in mice without overt toxicity.
Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with antiproliferative and antimetastatic activities in human cancer cells
Ling, Yong,Guo, Jing,Yang, Qiuxing,Zhu, Peng,Miao, Jiefei,Gao, Weijie,Peng, Yanfu,Yang, Jiaying,Xu, Kun,Xiong, Biao,Liu, Gongqing,Tao, Jinhua,Luo, Lin,Zhu, Qing,Zhang, Yanan
, p. 398 - 409 (2018/01/01)
A series of novel β-carboline-based hydroxamate derivatives 12a-k were designed and synthesized, and their biological activities in a series of in vitro assays were evaluated. Several of these β-carboline derivatives not only showed excellent HDAC1/3/6 inhibitory effects, but also displayed significant antitumor activities against five human cancer cells. The most potent compound 12f demonstrated the highest anticancer potency against cancer cell lines with IC50 values of 0.53–1.56 μM, which was considerably more potent than harmine (IC50 = 46.7–55.3 μM) and also three-to ten-fold lower than that of SAHA (IC50 = 4.48–6.26 μM). Immunoblot analysis revealed that 12f dose-dependently inhibited histone H3 and α-tubulin acetylation, confirming its HDAC inhibitory effects. Moreover, 12f significantly arrested HepG2 cells at G2/M phase through inhibiting cell cycle related protein CDK1 and cyclin B in a concentration dependent manner. Interestingly, 12f also exerted strong anti-metastasis activity by simultaneously reducing the protein level of MMP2 and MMP9 and inhibiting MAPK signaling pathway.
Microwave accelerated Pictet-Spengler reactions of tryptophan with ketones directed toward the preparation of 1,1-disubstituted indole alkaloids
Kuo, Fu-Ming,Tseng, Ming-Chung,Yen, Ya-Hew,Chu, Yen-Ho
, p. 12075 - 12084 (2007/10/03)
Using the Pictet-Spengler reactions of tryptophan with aldehydes under acidic conditions at ambient temperature, diastereoisomers of 1,3-disubstituted-1,2,3,4-tetrahydro-β-carbolines could readily be furnished in short time (0.5-4 h) with good to excellent yields (50-98%). Though intrinsically slow in reaction rates, ketone reactions can be accelerated (from days to minutes) using microwaves in open vessels with high isolated yields (67-99%), making those carbolines feasible reaction intermediates for the synthesis of both natural and unnatural indole alkaloids. Preparation of two indole alkaloids, tetrahydro-β-carbolinediketopiperazines and tetrahydro-β-carbolinehydantoins, were briefly discussed. Graphical Abstract
