22934-59-4Relevant articles and documents
Asymmetric total synthesis of four bioactive lignans using donor-acceptor cyclopropanes and bioassay of (?)- and (+)-niranthin against hepatitis B and influenza viruses
Karasawa, Daichi,Nishii, Yoshinori,Oshima, Mizuki,Ota, Ryotaro,Shimasaki, Noriko,Watashi, Koichi
, p. 4635 - 4639 (2022/02/19)
The asymmetric total synthesis of four lignans, dimethylmatairesinol, matairesinol, (?)-niranthin, and (+)-niranthin has been achieved using reductive ring-opening of cyclopropanes. Moreover, we performed bioassays of the synthesized (+)- and (?)-niranthins using hepatitis B and influenza viruses, which revealed the relationship between the enantiomeric structure and the anti-viral activity of niranthin.
Design, synthesis and biochemical evaluation of novel 2-amino-3-(7-methoxybenzo[d][1,3]dioxol-5-yl)propanoic acid using Horseradish peroxidase (HRP) activity, cellular ROS inhibition and molecular docking study
Demonceau, Albert,Etsè, Koffi Sénam,Mouithys-Mickalad, Ange,Serteyn, Didier,Zaragoza, Guillermo
, (2021/10/29)
In this paper, we report the design, synthesis and biochemical evaluation of 2-amino-3-(7-methoxybenzo[d][1,3]dioxol-5-yl)propanoic acid 9, a myristicin derivative, from cheap and available vanillin as starting material. Compound 9 is identified as a potential precursor of natural brasiliamide derivatives. All the products are fully characterized. The crystal structure of the intermediate diethyl 2-acetamido-2-((7-methoxybenzo[d][1,3]dioxol-5-yl)methyl)malonate 16, a precursor of this amino acid, is obtained and presented. The interactions stabilizing the crystal packing of 16 were deeply analyzed by considering first the supramolecular stacking and finally, by analyzing the contacts descriptors on the Hirshfeld surface, the molecular fingerprint and the intermolecular energy. Different biochemical properties of the desired amino acid 9 and its selected precursors are investigated. In DPPH test, 9 showed the best anti-radical activity (IC50 = 80.91 μM). The enzymatic, HRP-H2O2/L012, chemiluminescence assay reveals excellent inhibitory effect on the peroxidase activity and a good antioxidant activity of all the tested compounds with the best activity for 9 (IC50 = 0.36 μM). The anti-peroxidase activity observed for compound 9 was confirmed by molecular docking exploration that allows to identify interactions in the HRP-9 complex. Docking results showed that 9 interacts with catalytic and active site residues, especially with Arg38, His42, Ser73, Phe68 and Pro139. Moreover, the inhibition of ROS production by activated HL-60 cells was moderately obtained with compounds 9 and 13. The MTS cell viability test reveals that all tested compounds, except myristicin aldehyde 13, were not cytotoxic indicating that the observed inhibition of ROS production of activated HL-60 cells was not due to cells death. Finally, physicochemical and ADME-Tox predictions suggested that compound 9 could be considered as promising drug candidate.
Methanol as hydrogen source: Transfer hydrogenation of aromatic aldehydes with a rhodacycle
Aboo, Ahmed H.,Bennett, Elliot L.,Deeprose, Mark,Robertson, Craig M.,Iggo, Jonathan A.,Xiao, Jianliang
supporting information, p. 11805 - 11808 (2018/11/10)
A cyclometalated rhodium complex has been shown to perform highly selective and efficient reduction of aldehydes, deriving the hydrogen from methanol. With methanol as both the solvent and hydrogen donor under mild conditions and an open atmosphere, a wide range of aromatic aldehydes were reduced to the corresponding alcohols, without affecting other functional groups.
Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents
Semenova, Marina N.,Demchuk, Dmitry V.,Tsyganov, Dmitry V.,Chernysheva, Natalia B.,Samet, Alexander V.,Silyanova, Eugenia A.,Kislyi, Victor P.,Maksimenko, Anna S.,Varakutin, Alexander E.,Konyushkin, Leonid D.,Raihstat, Mikhail M.,Kiselyov, Alex S.,Semenov, Victor V.
, p. 700 - 721 (2019/01/03)
A series of both novel and reported combretastatin analogues, including diarylpyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles, were synthesized via improved protocols to evaluate their antimitotic antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure-activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0.25, 1, and 0.5 nM, respectively. These agents exhibited comparable cytotoxicity against human cancer cells. Structure-activity relationship studies revealed that compounds substituted with 3,4,5-trimethoxyphenyl ring A and 4-methoxyphenyl ring B displayed the highest activity. 3-Hydroxy group in the ring B was essential for the antiproliferative activity in the diarylisoxazole series, whereas it was not required for potency of diarylpyrazoles. Isoxazoles 3 with 3,4,5-trimethoxy-substituted ring A and 3-hydroxy-4-methoxy-substituted ring B were more active than the respective pyrazoles 1. Of the azoles substituted with the same set of other aryl pharmacophores, diarylpyrazoles 1, 4,5-diarylisoxazoles 3, and 4,5-diaryl-1,2,3-triazoles 7 displayed similar strongest antimitotic antitubulin effect followed by 3,4-diarylisoxazoles 5, 1,5-diaryl-1,2,3-triazoles 8, and pyrroles 10 that showed the lowest activity. Introduction of the amino group into the heterocyclic core decreased the antimitotic antitubulin effect of pyrazoles, triazoles, and to a lesser degree of 4,5-diarylisoxazoles, whereas potency of the respective 3,4-diarylisoxazoles was increased.
Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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, (2015/09/22)
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
Cis -restricted 3-aminopyrazole analogues of combretastatins: Synthesis from plant polyalkoxybenzenes and biological evaluation in the cytotoxicity and phenotypic sea urchin embryo assays
Tsyganov, Dmitry V.,Konyushkin, Leonid D.,Karmanova, Irina B.,Firgang, Sergei I.,Strelenko, Yuri A.,Semenova, Marina N.,Kiselyov, Alex S.,Semenov, Victor V.
, p. 1485 - 1491 (2013/09/23)
We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl- 3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds 12a and 14a displayed pronounced cytotoxicity in the NCI60 anticancer drug screen, with the ability to inhibit growth of multi-drug-resistant cancer cells.
COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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, (2012/04/23)
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
ANALGESIC THAT BINDS FILAMIN A
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Page/Page column 125, (2010/05/14)
A compound, composition and method are disclosed that can provide analgesia. A contemplated compound has a structure that corresponds to Formula A, wherein A, B, X, R1, R2, R7 and R8, and the dashed lines are defined within.
Total synthesis of graphislactones A, C, D, and H, of ulocladol, and of the originally proposed and revised structures of graphislactones e and F
Altemoeller, Martina,Gehring, Timo,Cudaj, Judith,Podlech, Joachim,Goesmann, Helmut,Feldmann, Claus,Rothenberger, Alexander
experimental part, p. 2130 - 2140 (2009/09/29)
Graphislactones A-H and the structurally related ulocladol are highly oxygenated resorcylic lactones produced by lichens and fungi. We present total syntheses of graphislactones A, C-F, H and of ulocladol. Graphislactones E, F, and H were synthesized for the first time. The spectra of graphislactones E and F synthesized as the originally proposed structures were not in agreement with published data. Consequently, revised structures for these compounds are proposed, whose correctness is unambiguously proven by total synthesis and comparison of the spectroscopic data. Key steps in all syntheses are Suzuki couplings for the construction of the central biaryl bond and Dakin reactions to supply further hydroxy groups required in these highly oxygenated substrates. Graphislactones A, C, and H, acylated graphislac- tone D and ulocladol were prepared in 8-11 steps with 7-20% yield starting with purchasable compounds, where the longest linear sequence consists of 5-9 steps. The syntheses are thus significantly shorter than the previously published syntheses of graphislactones A-D and of ulocladol. Graphis- lactones E and F were synthesized in 8 steps, where the longest linear sequences consist of 6 and 5 steps, respectively. They were isolated as the respective acetylated compounds with 25 and 10% yield.
Antineoplastic agents. 578. synthesis of stilstatins 1 and 2 and their water-soluble prodrugs
Pettit, George R.,Thornhill, Andrew,Melody, Noeleen,Knight, John C.
experimental part, p. 380 - 388 (2009/12/04)
Efficient syntheses of 3,4-methylenedioxy-4′,5-dimethoxy-2′, 3′-dihydroxy-Z-stilbene (stilstatin 1, 2), 3,4,4′-trimethoxy- 2′,3′,5-trihydroxy-Z-stilbene (stilstatin 2, 5), and respective phosphate prodrugs have been summarized. Both 2 and 5 were accessed via a convergent step synthesis using phosphonium bromides 6 and 21 in Wittig reactions with 2,3- bis(tert-butyldimethylsilyloxy)-4′-methoxybenzaldehyde 14. Deprotection of silyl ethers 15 and 26 with TBAF furnished 2 and 5, respectively. Phosphorylation of 2 and 5 afforded the phosphoric acid intermediates 17 and 28 for prodrug development. These phosphoric acid precursors were employed in parallel series of reactions to produce a selection of metal cation prodrug candidates. The biological activities of stilstatins 1 (2)and2(5) and their respective prodrugs were evaluated against a panel of one murine (P388) and six human cancer cell lines. Compared to combretastatin A-2 (1), stilstatin 1 (2) has an additional vicinal hydroxy group on the B ring, the presence of which was detrimental to the cancer cell line potency; in vivo, however, compound 2 would be predicted to have greater anticancer activity resulting from the o-quinone mechanism of action analogous to that of combretastatin A-1 (4). The substitution of a hydroxy group for a methoxy group on the A ring of combretastatin A-1 (4), resulting in stilstatin 2 (5), gave rise to a modest level of inhibition consistent with that found for 4 against cancer cell lines.
