19676-64-3Relevant articles and documents
A short synthesis of (±)-antroquinonol in an unusual scaffold of 4-hydroxy-2-cyclohexenone
Hsu, Che-Sheng,Chou, Ho-Hsuan,Fang, Jim-Min
, p. 5510 - 5519 (2015)
Antroquinonol, which was first isolated from a mushroom, Antrodia cinnamomea, found in Taiwan, is an anticancer compound with a unique core structure of 4-hydroxy-2,3-dimethoxycyclohex-2-enone carrying methyl, farnesyl and hydroxyl substituents in the 4,5-cis-5,6-trans configuration. A short synthesis of (±)-antroquinonol is accomplished in seven steps from 2,3,4-trimethoxyphenol, which is oxidized in methanol to a highly electron-rich substrate of 2,3,4,4-tetramethoxycyclohexadienone and then a Michael reaction with dimethylcuprate is performed as the key step, followed by alkylation, reduction and epimerization to incorporate the required substituents at three contiguous stereocenters.
Studies toward the development of antiproliferative neoclerodanes from salvinorin A
Vasiljevik, Tamara,Groer, Chad E.,Lehner, Kurt,Navarro, Hernan,Prisinzano, Thomas E.
, p. 1817 - 1824 (2014)
The success rate for central nervous system (CNS) drug candidates in the clinic is relatively low compared to the industry average across other therapeutic areas. Penetration through the blood-brain barrier (BBB) to reach the therapeutic target is a major obstacle in development. The rapid CNS penetration of salvinorin A has suggested that the neoclerodane nucleus offers an excellent scaffold for developing antiproliferative compounds that enter the CNS. The Liebeskind-Srogl reaction was used as the main carbon-carbon bond-forming step toward the synthesis of quinone-containing salvinorin A analogues. Quinone-containing salvinorin A analogues were shown to have antiproliferative activity against the MCF7 breast cancer cell line, but show no significant activity at the κ-opioid receptors. In an in vitro model of BBB penetration, quinone-containing salvinorin A analogues were shown to passively diffuse across the cell monolayer. The analogues, however, are substrates of P-glycoprotein, and thus further modification of the molecules is needed to reduce the affinity for the efflux transporter.
Total Synthesis of Dactylicapnosines A and B
Zhao, Yinjiao,Li, Yuda,Wang, Bei,Zhao, Jingfeng,Li, Liang,Luo, Xiao-Dong,Zhang, Hongbin
, p. 13772 - 13778 (2020)
Dactylicapnosines A and B, two natural products from Dactylicapnos scandens, exhibited potent anti-inflammatory and analgesic activities both in vitro and in vivo. In this paper, we report our second-generation synthesis of dactylicapnosine A and the first total synthesis of dactylicapnosine B. Our synthetic route features acid-induced isomerization of o-quinone (16), Co-mediated regioselective ring contraction of p-quinone (8b), and oxidative methoxylation of enone (18). This modified sequence provides dactylicapnosine A in 14 steps with an overall yield of 12% from a known compound (14a) and also offers opportunities to synthesize dactylicapnosine-like analogues for biological investigations.
Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming
Chen, Yuwen,Huang, Yulan,Jiao, Wei,Li, Fu,Li, Suiyan,Li, Wenhua,Lin, Yuan,Liu, Wanli,Ma, Yuling,Sheng, Yuwen,Suksamrarn, Apichart,Wang, Fei,Wang, Jing,Wei, Xiao,Wisanwattana, Wisanee,Wu, Wenbi,Zeng, Zhongqiu,Zhang, Guolin,Zhang, Jichao,Zhu, Qiyu
, (2022/01/03)
Cancer cell proliferation in some organs often depends on conversion of pyruvate to oxaloacetate via pyruvate carboxylase (PC) for replenishing the tricarboxylic acid cycle to support biomass production. In this study, PC was identified as the cellular target of erianin using the photoaffinity labeling-click chemistry-based probe strategy. Erianin potently inhibited the enzymatic activity of PC, which mediated the anticancer effect of erianin in human hepatocellular carcinoma (HCC). Erianin modulated cancer-related gene expression and induced changes in metabolic intermediates. Moreover, erianin promotes mitochondrial oxidative stress and inhibits glycolysis, leading to insufficient energy required for cell proliferation. Analysis of 14 natural analogs of erianin showed that some compounds exhibited potent inhibitory effects on PC. These results suggest that PC is a cellular target of erianin and reveal the unrecognized function of PC in HCC tumorigenesis; erianin along with its analogs warrants further development as a novel therapeutic strategy for the treatment of HCC.
Rational design, synthesis and biological evaluation of ubiquinone derivatives as IDO1 inhibitors
Ding, Yuyang,Tang, Fei,Xue, Xiaoqian,Luo, Jinfeng,Hussain, Muzammal,Huang, Yanhui,Wang, Zhen,Jiang, Hao,Tu, Zhengchao,Zhang, Jiancun
supporting information, (2019/05/21)
Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive therapeutic target for the treatment of cancer, chronic viral infections and neurological disorders characterized by pathological immune stimulation. Herein, a series of known metal-chelating ubiquinone derivatives were designed, synthesized and evaluated for the IDO1 inhibiting activities. The docking studies showed that the compounds 11, 16, 18 and coenzyme-Q1 exhibited different binding modes to IDO1 protein. Among these compounds, the most active compound is 16d with an IC50 of 0.13 μM in enzymatic assay. The results reveal that a possible halogen bonding interaction between the bromine atom (3-Br) and Cys129 significantly enhances the inhibition activity against IDO1. This study provides structural insights of the interactions between ubiquinone analogues and IDO1 protein for the further modification and optimization.
