59481-63-9Relevant articles and documents
Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming
Sheng, Yuwen,Chen, Yuwen,Zeng, Zhongqiu,Wu, Wenbi,Wang, Jing,Ma, Yuling,Lin, Yuan,Zhang, Jichao,Huang, Yulan,Li, Wenhua,Zhu, Qiyu,Wei, Xiao,Li, Suiyan,Wisanwattana, Wisanee,Li, Fu,Liu, Wanli,Suksamrarn, Apichart,Zhang, Guolin,Jiao, Wei,Wang, Fei
, p. 460 - 484 (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.
NOVEL SMALL MOLECULE DRUG CONJUGATES OF GEMCITABINE DERIVATIVES
-
, (2019/08/26)
Disclosed are compounds having formula (I) or a pharmaceutically acceptable salt, ester, amide, solvate, or stereoisomer thereof, wherein L, Y1, Y2, Y3, Y4, Y5, Z1, Z2, Z3, Z4, Z5, Z6, and Effector are each as defined in the specification; compositions thereof; uses thereof; and methods of use thereof.
SMALL MOLECULE DRUG CONJUGATES OF GEMCITABINE MONOPHOSPHATE
-
, (2019/08/26)
Disclosed are compounds having formula (I): or a pharmaceutically acceptable salt, ester, amide, solvate, or stereoisomer thereof, wherein L, Y1, Y2, Y3, Y4, Y5, Z1, Z2, Z3, Z4, Z5, Z6 are each as defined in the specification; compositions thereof; uses thereof; and methods of use thereof.
Antimitotic and vascular disrupting agents: 2-Hydroxy-3,4,5- trimethoxybenzophenones
Chang, Chih-Yi,Chuang, Hsun-Yueh,Lee, Hsueh-Yun,Yeh, Teng-Kuang,Kuo, Ching-Chuan,Chang, Chi-Yen,Chang, Jang-Yang,Liou, Jing-Ping
, p. 306 - 314 (2014/04/03)
2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC 50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.
Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2 H -chromene derivatives as potent anti-breast cancer agents
Rahmani-Nezhad, Samira,Safavi, Maliheh,Pordeli, Mahboobeh,Ardestani, Sussan Kabudanian,Khosravani, Leila,Pourshojaei, Yaghoub,Mahdavi, Mohammad,Emami, Saeed,Foroumadi, Alireza,Shafiee, Abbas
, p. 562 - 569 (2015/01/09)
A series of 2-aryl-3-nitro-2H-chromenes 4a-u were designed as hybrid analogs of flavanone, β-nitrostyrene and nitrovinylstilbene scaffolds. They were synthesized from the reaction of appropriate β-nitrostyrenes and salicylaldehydes in good yields. In vitro cytotoxic activities of compounds 4a-u were tested against breast cancer cell lines including MCF-7, T-47D and MDA-MB-231. Most compounds exhibited good cytotoxic activity against selected cell lines, being more potent than standard drug etoposide. Representatively, 8-methoxy-3-nitro-2-(4-chlorophenyl)-2H-chromene (4l) with IC50 Combining double low line 0.2 μ4M against MCF-7 cells, was 36-times more potent than etoposide. Apoptosis as a mechanism of cell death for selected compounds 4h and 4l was confirmed morphologically by acridine orange/ethidium bromide double staining and TUNEL analysis, as well as caspase-3 activation assay.
Total synthesis of six 3,4-unsubstituted coumarins
Gao, Wenqing,Li, Qingyong,Chen, Jian,Wang, Zhichao,Hua, Changlong
, p. 15613 - 15623 (2014/01/17)
In this article we describe a new methodology for the total synthesis of 3,4-unsubstituted coumarins from commercially available starting materials. Six examples were prepared, including five naturally occurring coumarins-7-hydroxy- 6,8-dimethoxycoumarin (isofraxidin), 7-hydroxy-6-methoxycoumarin (scopoletin), 6,7,8-trimethoxycoumarin, 6,7-dimethoxycoumarin (scoparone), and 7,8-dihydroxycoumarin (daphnetin) and one synthetic coumarin, 7-hydroxy-6-ethoxycoumarin. Moreover, five important o-hydroxybenzaldehyde intermediates were also obtained, namely 2,4-dihydroxy-3,5- dimethoxybenzaldehyde, 2,4-dihydroxy-5-methoxybenzaldehyde, 5-ethoxy-2,4- dihydroxybenzaldehyde, 2-hydroxy-3,4,5-trimethoxybenzaldehyde, and 2-hydroxy-4,5-dimethoxybenzaldehyde. The method developed herein involves just three or four steps and allows for the rapid synthesis of these important molecules in excellent yields. This is the first synthesis of 6,7,8-trimethoxycoumarin and 7-hydroxy-6-ethoxycoumarin.
An alternative route for the synthesis of 2,3,4,5-tetramethoxytoluene
Vera, William J.,Chinea, Kimberly,Banerjee, Ajoy K.
experimental part, p. 186 - 187 (2009/10/15)
The transformation of the commercially available 2,3,4- trimetho×ybenzaldehyde to 2,3,4,5-tetrametho×ytoluene using a Dakin reaction to insert the extra oxygen, formylation, reduction and methylation of the phenolic hydro×yl group is described.
Total synthesis of polemannones B and C
Fadeyi, Olugbeminiyi O.,Nathan Daniels,DeGuire, Sean M.,Lindsley, Craig W.
body text, p. 3084 - 3087 (2009/10/04)
The first total synthesis of polemannones B and C, higly oxygenated benzoxanthenones derivatives from Polemannia montana, is reported employing our new catalytic Cu(II)/sparteine system for β,β-phenolic couplings and tandem inverse-electron demand Diels-Alder reaction cascade in 75-90% yield.
Nucleophilic substitution of nitro groups by [18F]fluoride in methoxy-substituted ortho-nitrobenzaldehydes-A systematic study
Shen, Bin,L?ffler, Dirk,Reischl, Gerald,Machulla, Hans-Jürgen,Zeller, Klaus-Peter
experimental part, p. 216 - 224 (2009/07/25)
As model reactions for the introduction of [18F]fluorine into aromatic amino acids, the replacement of NO2 by [18F]fluoride ion in mono- to tetra-methoxy-substituted ortho-nitrobenzaldehydes was systematically investigated. Unexpectedly, the highly methoxylated precursors 2,3,4-trimethoxy-6-nitrobenzaldehyde and 2,3,4,5-tetramethoxy-6-nitrobenzaldehyde showed high maximum radiochemical yields (82% and 48% respectively). When the electrophilicity of the leaving group substituted carbon atom is expressed by its 13C NMR chemical shift a good correlation with the reaction rate at the beginning of the reaction (first min) was found (R2 = 0.89), whereas the maximum radiochemical yields correlated much poorer with this electrophilicity parameter. This may be caused by side reactions becoming influencial in the further reaction course. As possible side reactions the demethylation of methoxy groups and intramolecular redox reactions could be detected by HPLC/MS.
Novel cyclopropapyrroloindole derivative (AT-3510) bearing methoxycarbonyl and trifluoromethyl groups
Fukuda, Yasumichi,Furuta, Hirosuke,Kusama, Yoshie,Ebisu, Hiroyuki,Oomori, Yasuo,Terashima, Shiro
, p. 1448 - 1458 (2007/10/03)
The seco-Cl 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) derivatives dl- and/or (S)-10 carrying various acyl moleties at the N6-position were synthesized along with their prodrugs (S)-12, and their antitumor activity was evaluated. Among these derivatives, AT-3510 [(S)- 12m], the novel prodrug MCTFCPI derivative carrying a 5-(7- methoxybenzofuran-2-ylcarbonyl)aminoindole-2-carbonyl group at the N6- position, was found to exhibit more excellent antitumor activity against human tumor xenografts than the clinical trial candidates carzelesin (6) and KW-2189 (7) and cisplatin.
