24131-30-4Relevant articles and documents
Synthesis of (E)-2,3′,4,5′-tetramethoxy[2-11C] stilbene
Schweiger, Lutz,Craib, Stuart,Welch, Andrew,Smith, Tim A. D.
, p. 1206 - 1210 (2007)
In this paper, we describe the radiosynthesis of the compound (E)-2,3′,4,5′-tetramethoxy[2-11C]stilbene, a potential, universal tumour positron emission tomography imaging agent. The production of (E)-2,3′,4,5′-tetramethoxy[2-11C]sti
Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters
Frydrych, Ivo,Urban, Milan,?arek, Jan,Benická, Sandra,D?ubák, Petr,Gurská, Soňa,Hajdúch, Marián,Kotulová, Jana,Li?ková, Barbora,Olejníková, Denisa,Pokorny, Jan
, (2021/07/28)
A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Compounds 4.22, 4.30, 4.33, 4.39 had IC50 below 5 μmol/L; 4.22 and 4.39 were selected for studies of the mechanism of action. Cell cycle analysis revealed an increase in the number of apoptotic cells at 5 × IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both 4.22 and 4.39 led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 × IC50 and almost complete inhibition at 5 × IC50. Interestingly, compound 4.39 at 5 × IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations. Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds 4.22 and 4.39 trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacological parameters of derivative 4.22 were superior to 4.39, therefore 4.22 was the finally selected candidate for the development of anticancer drug.
FGFR4 INHIBITORS
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, (2016/10/31)
Methods, compounds, pharmaceutical compositions, and methods of preparing medicaments for treating hepatocellular carcinoma having an altered FGFR4 and/or FGF19 status.
NOVEL FUNCTIONALIZED 1,3-BENZENE DIOLS AND THEIR METHOD OF USE FOR THE TREATMENT OF HEPATIC ENCEPHALOPTHY
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Paragraph 0317-0318, (2016/11/14)
Pharmaceutical compositions of the invention include novel functionalized 1,3-benzenediols having a disease-modifying action in the treatment of hepatic encephalopathy and related conditions. Pharmaceutical compositions of the invention further include novel neuroprotective agents.
Styrylphenylphthalimides as Novel Transrepression-Selective Liver X Receptor (LXR) Modulators
Nomura, Sayaka,Endo-Umeda, Kaori,Aoyama, Atsushi,Makishima, Makoto,Hashimoto, Yuichi,Ishikawa, Minoru
supporting information, p. 902 - 907 (2015/08/24)
Anti-inflammatory effects of liver X receptor (LXR) ligands are thought to be largely due to LXR-mediated transrepression, whereas side effects are caused by activation of LXR-responsive gene expression (transactivation). Therefore, selective LXR modulators that preferentially exhibit transrepression activity should exhibit anti-inflammatory properties with fewer side effects. Here, we synthesized a series of styrylphenylphthalimide analogues and evaluated their structure-activity relationships focusing on LXRs-transactivating-agonistic/antagonistic activities and transrepressional activity. Among the compounds examined, 17l showed potent LXR-transrepressional activity with high selectivity over transactivating activity and did not show characteristic side effects of LXR-transactivating agonists in cells. This representative compound, 17l, was confirmed to have LXR-dependent transrepressional activity and to bind directly to LXRβ. Compound 17l should be useful not only as a chemical tool for studying the biological functions of LXRs transrepression but also as a candidate for a safer agent to treat inflammatory diseases.
A Scalable biomimetic synthesis of resveratrol dimers and systematic evaluation of their antioxidant activities
Matsuura, Bryan S.,Keylor, Mitchell H.,Li, Bo,Lin, Yuxuan,Allison, Shelby,Pratt, Derek A.,Stephenson, Corey R. J.
supporting information, p. 3754 - 3757 (2015/03/18)
An efficient synthetic route to the resveratrol oligomers quadrangularin A and pallidol is reported. It features a scalable biomimetic oxidative dimerization that proceeds in excellent yield and with complete regioselectivity. A systematic evaluation of t
Identification of novel ROS inducers: Quinone derivatives tethered to long hydrocarbon chains
Hong, Yeonsun,Sengupta, Sandip,Hur, Wooyoung,Sim, Taebo
, p. 3739 - 3750 (2015/05/27)
We performed the first synthesis of the 17-carbon chain-tethered quinone moiety 22 (SAN5201) of irisferin A, a natural product exhibiting anticancer activity, and its derivatives. We found that 22 is a potent ROS inducer and cytotoxic agent. Compound 25 (SAN7401), the hydroquinone form of 22, induced a significant release of intracellular ROS and apoptosis (EC50 = 1.3-2.6 μM) in cancer cell lines, including A549 and HCT-116. Compared with the activity of a well-known ROS inducer, piperlongumine, 22 and 25 showed stronger cytotoxicity and higher selectivity over noncancerous cells. Another hydroquinone tethering 12-carbon chain, 26 (SAN4601), generated reduced levels of ROS but showed more potent cytotoxicity (EC50 = 0.8-1.6 μM) in cancer cells, although it lacked selectivity over noncancerous cells, implying that the naturally occurring 17-carbon chain is also crucial for ROS production and a selective anticancer effect. Both 25 and 26 displayed strong, equipotent activities against vemurafenib-resistant SK-Mel2 melanoma cells and p53-deficient H1299 lung cancer cells as well, demonstrating their broad therapeutic potential as anticancer agents.
NOVEL FUNCTIONALIZED 1,3-BENZENE DIOLS AND THEIR METHOD OF USE FOR THE TREATMENT OF HEPATIC ENCEPHALOPATHY
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Paragraph 00278-00279, (2015/07/23)
Pharmaceutical compositions of the invention include novel functionalized 1,3-benzenediols having a disease-modifying action in the treatment of hepatic encephalopathy and related conditions. Pharmaceutical compositions of the invention further include novel neuroprotective agents.
Novel resveratrol-based substrates for human hepatic, renal, and intestinal UDP-glucuronosyltransferases
Greer, Aleksandra K.,Madadi, Nikhil R.,Bratton, Stacie M.,Eddy, Sarah D.,Mazerska, Zofia,Hendrickson, Howard P.,Crooks, Peter A.,Radominska-Pandya, Anna
, p. 536 - 545 (2014/05/06)
Trans-Resveratrol (tRes) has been shown to have powerful antioxidant, anti-inflammatory, anticarcinogenic, and antiaging properties; however, its use as a therapeutic agent is limited by its rapid metabolism into its conjugated forms by UDP-glucuronosyltransferases (UGTs). The aim of the current study was to test the hypothesis that the limited bioavailability of tRes can be improved by modifying its structure to create analogs which would be glucuronidated at a lower rate than tRes itself. In this work, three synthetic stilbenoids, (E)-3-(3-hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid (NI-12a), (E)-2,4-dimethoxy-6-(4-methoxystyryl)benzaldehyde oxime (NI-ST-05), and (E)-4-(3,5-dimethoxystyryl)-2,6-dinitrophenol (DNR-1), have been designed based on the structure of tRes and synthesized in our laboratory. UGTs recognize and glucuronidate tRes at each of the 3 hydroxyl groups attached to its aromatic rings. Therefore, each of the above compounds was designed with the majority of the hydroxyl groups blocked by methylation and the addition of other novel functional groups as part of a drug optimization program. The activities of recombinant human UGTs from the 1A and 2B families were examined for their capacity to metabolize these compounds. Glucuronide formation was identified using HPLC and verified by β-glucuronidase hydrolysis and LC-MS/MS analysis. NI-12a was glucuronidated at both the -COOH and -OH functions, NI-ST-05 formed a novel N-O-glucuronide, and no product was observed for DNR-1. NI-12a is primarily metabolized by the hepatic and renal enzyme UGT1A9, whereas NI-ST-05 is primarily metabolized by an extrahepatic enzyme, UGT1A10, with apparent Km values of 240 and 6.2 μM, respectively. The involvement of hepatic and intestinal UGTs in the metabolism of both compounds was further confirmed using a panel of human liver and intestinal microsomes, and high individual variation in activity was demonstrated between donors. In summary, these studies clearly establish that modified, tRes-based stilbenoids may be preferable alternatives to tRes itself due to increased bioavailability via altered conjugation.
Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer activity
Parihar, Swati,Kumar, Amit,Chaturvedi, Amit K.,Sachan, Naresh Kumar,Luqman, Suaib,Changkija, Bendangla,Manohar, Murli,Prakash, Om,Chanda,Khan, Feroz,Chanotiya,Shanker, Karuna,Dwivedi, Anila,Konwar, Rituraj,Negi, Arvind S.
, p. 332 - 344 (2013/11/19)
Combretastatin A4 analogues were synthesized on steroidal framework from gallic acid with a possibility of anti-breast cancer agents. Twenty two analogues were synthesized and evaluated for cytotoxicity against human breast cancer cell lines (MCF-7 & MDA-MB 231). The best analogue 22 showed potent antitubulin effect. Docking experiments also supported strong binding affinity of 22 to microtubule polymerase. In cell cycle analysis, 22 induced apoptosis in MCF-7 cells significantly. It was found to be non-toxic up to 300 mg/kg dose in Swiss albino mice in acute oral toxicity. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".
