5470-37-1Relevant articles and documents
Synthesis method of chloroindole hydrazide
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Paragraph 0065-0068, (2022/03/18)
The invention relates to a synthesis method of chloroindole hydrazide, and belongs to the technical field of pesticides. The specific preparation method comprises the following steps: (1) uniformly mixing a compound shown as a formula (I), a solvent I, acetonitrile and a catalyst I, and then adding a hydrogen source for reaction; after the reaction is finished, treating to obtain a compound shown as a formula (II); (2) mixing the compound shown in the formula (II), (4-chlorphenyl) methylene hydrazine, a solvent II and a catalyst II for reaction, and after the reaction is completed, performing post-treatment to obtain chloroindole hydrazide; a novel synthetic route is provided, catalytic hydrogenation cyclization is performed on tryptophan or ester thereof and acetonitrile, and then reacts with (4-chlorphenyl) methylene hydrazine to obtain the chloroindole hydrazide through two steps. Compared with the prior art, the preparation method has the advantages of short synthesis steps, high reaction yield, no use of high-toxicity, strong-corrosivity and strong-irritation reagents, and convenience in realization of industrial production.
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.
β-Carboline and N-hydroxycinnamamide hybrids as anticancer agents for drug-resistant hepatocellular carcinoma
Ling, Yong,Gao, Wei-Jie,Ling, Changchun,Liu, Ji,Meng, Chi,Qian, Jianqiang,Liu, Siqun,Gan, Huiling,Wu, Hongmei,Tao, Jinhua,Dai, Hong,Zhang, Yanan
, p. 515 - 526 (2019/03/08)
In an effort to develop anticancer agents that may overcome drug resistance, the number one reason in caner death, we have developed a series of novel hybrids of β-carboline and N-hydroxycinnamamide as histone deacetylase (HDAC) inhibitors. Most of the hybrids 13a-p showed strong antiproliferative effects with low-micromolar IC50 values against four human cancer cells. The most potent compound of series 13p exhibited high HDAC1/6 inhibitory effects, and also increased the acetylation levels of histone H3, H4 and α-tubulin. Importantly, 13p demonstrated high anticancer potency against drug-sensitive HepG2 and Bel7402 cells and drug-resistant Bel7402/5FU cells. Hybrid 13p triggered significant apoptosis by regulating apoptotic relative proteins expression in these Bel7402/5FU cells. Finally, 13p induced a substantial amount of autophagic flux activity by the accretion of the expression of LC3-II and the degeneration of expression of p62 and LC3-I in Bel7402/5FU cells. Overall, 13p is a novel β-carboline/N-hydroxycinnamamide hybrid with significant anticancer potency that warrants further evaluation for the treatment of drug-resistant hepatocellular carcinoma.
