299181-75-2Relevant articles and documents
Potent hydrazone derivatives targeting esophageal cancer cells
Li, Ling-Yu,Peng, Jia-Di,Zhou, Wenjuan,Qiao, Hui,Deng, Xin,Li, Zhou-Hua,Li, Ji-Deng,Fu, Yun-Dong,Li, Song,Sun, Kai,Liu, Hong-Min,Zhao, Wen
, p. 359 - 371 (2018)
Hydrazone and their derivatives are a series of highly active molecules, which are widely used as lead compounds for the research and development of new anti-cancer drugs. In this study, 20 compounds were synthesized, based on this scaffold and their in vitro cytotoxicity against 6 cancer cell lines, including EC9706, SMMC-7721, MCF7, PC3, MGC-803 and EC109 was tested. Among them, compound 6p, showed strong anti-proliferative activities on esophageal carcinoma cells: EC9706 and EC109 with IC50 values of 1.09 ± 0.03 and 2.79 ± 0.45 μM, respectively. 6p also significantly induces both EC9706 and EC109 cell cycle arrest at G0/G1 phase and cell apoptosis, as well as intracellular ROS accumulation, which could be markedly reversed caspase or ROS inhibitor: NAC. Meanwhile, treatment of compound 6p results in significant declined mitochondria membrane potential, increases in the expression of P53 and bax, as well as decrease in Bcl-2. 6p also activates caspase-8/9/3, PARP and Bid, indicating that 6p induces cancer cell apoptosis via the death receptor-mediated extrinsic pathway and the mitochondria-mediated intrinsic pathway. Further studies also proved that 6p does not show obvious side effects at cellular and in vivo levels. Our findings suggested that hydrazone derivative: compound 6p may serve as a lead compound for further optimization against esophageal cancer cells.
Synthesis and biological evaluation of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides as potent LSD1 inhibitors
Zhou, Yang,Li, Yan,Wang, Wen-Jing,Xiang, Pu,Luo, Xin-Mei,Yang, Li,Yang, Sheng-Yong,Zhao, Ying-Lan
, p. 4552 - 4557 (2016/08/24)
Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is recognized as an attractive therapeutic target in multiple malignancies. In this study, a series of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides were synthesized and biologically evaluated for their potential LSD1 inhibitory effect. Among them, compounds 5a and 5n showed the most potent LSD1 inhibitory activity with IC50values of 1.4 and 1.7?nM, respectively, which were about 10 times more potent compared with (E)-N-(1-(5-chloro-2-hydroxyphenyl) ethylidene)-3-(morpholinosulf-only) benzohydrazide (J. Med. Chem. 2013, 56, 9496–9508; as reference compound). Compounds 5a and 5n also exhibited marked anti-proliferation activities against cancer cell lines that highly expressed LSD1. These results suggest that these optimized compounds might be served as promising LSD1 inhibitors against cancer, which merit further study.
High-throughput virtual screening identifies novel N ′-(1- phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors
Sorna, Venkataswamy,Theisen, Emily R.,Stephens, Bret,Warner, Steven L.,Bearss, David J.,Vankayalapati, Hariprasad,Sharma, Sunil
supporting information, p. 9496 - 9508 (2014/01/06)
Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is an attractive therapeutic target in multiple malignancies. Here we report a structure-based virtual screen of
