481-85-6Relevant articles and documents
Preparations of anthraquinone and naphthoquinone derivatives and their cytotoxic effects
Cui, Xing-Ri,Saito, Ryota,Kubo, Takatsugu,Kon, Daijiro,Hirano, Yuich,Saito, Setsuo
, p. 302 - 314 (2011)
Chrysophanol and 1,8-di-O-hexylchrysophanol derivatives having nucleic acid bases at position 5 were synthesized. Furthermore, derivatives of menadione substituted at position 11 (type A naphthoquinone derivatives) or methylmenadione substituted at position 7 (type B naphthoquinone derivatives) modified with nucleic acid bases, amines and thiocyano, selenocyano or thioacetyl groups were synthesized. The cytotoxic effects of these derivatives on HCT 116 cells, which poorly express P-glycoprotein (P-gp), and Hep G2 cells, which stably express P-gp, were evaluated by performing 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results were compared with those obtained using 5-fluorouracil (5-FU), which has been used clinically. Several of these derivatives exhibited markedly higher potent cytotoxic effects not only on HCT cancer cells but also Hep G2 cancer cells as compared with 5-FU.
Detection and quantification of vitamin K1 quinol in leaf tissues
Oostende, Chloe van,Widhalm, Joshua R.,Basset, Gilles J.C.
, p. 2457 - 2462 (2008)
Phylloquinone (2-methyl-3-phytyl-1,4-naphthoquinone; vitamin K1) is vital to plants. It is responsible for the one-electron transfer at the A1 site of photosystem I, a process that involves turnover between the quinone and semi-quinone forms of phylloquinone. Using HPLC coupled with fluorometric detection to analyze Arabidopsis leaf extracts, we detected a third redox form of phylloquinone corresponding to its fully reduced - quinol-naphthoquinone ring (PhQH2). A method was developed to quantify PhQH2 and its corresponding oxidized quinone (PhQ) counterpart in a single HPLC run. PhQH2 was found in leaves of all dicotyledonous and monocotyledonous species tested, but not in fruits or in tubers. Its level correlated with that of PhQ, and represented 5-10% of total leaf phylloquinone. Analysis of purified pea chloroplasts showed that these organelles accounted for the bulk of PhQH2. The respective pool sizes of PhQH2 and PhQ were remarkably stable throughout the development of Arabidopsis green leaves. On the other hand, in Arabidopsis and tomato senescing leaves, PhQH2 was found to increase at the expense of PhQ, and represented 25-35% of the total pool of phylloquinone. Arabidopsis leaves exposed to light contained lower level of PhQH2 than those kept in the dark. These data indicate that PhQH2 does not originate from the photochemical reduction of PhQ, and point to a hitherto unsuspected function of phylloquinone in plants. The putative origin of PhQH2 and its recycling into PhQ are discussed.
One-pot hydroacetylation of menadione (vitamin K3) to menadiol diacetate (vitamin K4) by heterogeneous catalysis
Dobrinescu, Claudiu,Iorgulescu, Elena E.,Mihailciuc, Constantin,MacOvei, Dan,Wuttke, Stefan,Kemnitz, Erhard,Parvulescu, Vasile I.,Coman, Simona M.
, p. 1301 - 1306 (2012)
Vitamin K4 (menadiol diacetate, MDD) can be easily synthesized through cleaner and more efficient catalytic alternatives following the green chemistry principles. Ionic gold-based hydroxylated fluorides are active bi-functional catalysts for the one-pot hydroacetylation of menadione leading to MDD with 77% selectivity. Unprecedent results were obtained in the presence of oxide-fluoride catalysts by using a microwave-assisted hydrogen-transfer (Meerwein-Ponndorf-Verley reaction) coupled with an acetylation approach, yielding very high selectivities for the target product (95%). Copyright
Reduction of quinones by NADH catalyzed by organoiridium complexes
Liu, Zhe,Deeth, Robert J.,Butler, Jennifer S.,Habtemariam, Abraha,Newton, Mark E.,Sadler, Peter J.
, p. 4194 - 4197 (2013)
One electron at a time: Half-sandwich organometallic cyclopentadienyl- IrIII complexes containing N,N-chelated ligands can catalyze the reduction of quinones (Q), such as vitaminK3, to semiquinones (Q .-) by coenzyme NADH (see picture). DFT calculations suggest that the mechanism involves hydride transfer followed by two one-electron transfers and the unusual IrII oxidation state as a key transient intermediate. Copyright
Synthesis of Novel Synthetic Vitamin K Analogues Prepared by Introduction of a Heteroatom and a Phenyl Group That Induce Highly Selective Neuronal Differentiation of Neuronal Progenitor Cells
Kimura, Kimito,Hirota, Yoshihisa,Kuwahara, Shigefumi,Takeuchi, Atsuko,Tode, Chisato,Wada, Akimori,Osakabe, Naomi,Suhara, Yoshitomo
, p. 2591 - 2596 (2017)
We synthesized novel vitamin K2 analogues that incorporated a heteroatom and an aromatic ring in the side chain and evaluated their effect on the selective differentiation of neuronal progenitor cells into neurons in vitro. The results showed that a menaquinone-2 analogue bearing a p-fluoroaniline had the most potent activity, which was more than twice as great as the control. In addition, the neuronal selectivity was more than 3 times greater than the control.
Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities
Sakane, Rie,Kimura, Kimito,Hirota, Yoshihisa,Ishizawa, Michiyasu,Takagi, Yuta,Wada, Akimori,Kuwahara, Shigefumi,Makishima, Makoto,Suhara, Yoshitomo
, p. 4881 - 4884 (2017)
Vitamin K is an essential cofactor of γ-glutamylcarboxylase as related to blood coagulation and bone formation. Menaquinone-4, one of the vitamin K homologues, is biosynthesized in the body and has various biological activities such as being a ligand for steroid and xenobiotic receptors, protection of neuronal cells from oxidative stress, and so on. From this background, we focused on the role of menaquinone in the differentiation activity of progenitor cells into neuronal cells and we synthesized novel vitamin K derivatives with modification of the ω-terminal side chain. We report here new vitamin K analogues, which introduced an alkylated phenyl group at the ω-terminal side chain. These compounds exhibited potent differentiation activity as compared to control.
A Synthetic Isoprenoid Lipoquinone, Menaquinone-2, Adopts a Folded Conformation in Solution and at a Model Membrane Interface
Koehn, Jordan T.,Magallanes, Estela S.,Peters, Benjamin J.,Beuning, Cheryle N.,Haase, Allison A.,Zhu, Michelle J.,Rithner, Christopher D.,Crick, Dean C.,Crans, Debbie C.
, p. 275 - 288 (2018)
Menaquinones (naphthoquinones, MK) are isoprenoids that play key roles in the respiratory electron transport system of some prokaryotes by shuttling electrons between membrane-bound protein complexes acting as electron acceptors and donors. Menaquinone-2 (MK-2), a truncated MK, was synthesized, and the studies presented herein characterize the conformational and chemical properties of the hydrophobic MK-2 molecule. Using 2D NMR spectroscopy, we established for the first time that MK-2 has a folded conformation defined by the isoprenyl side-chain folding back over the napthoquinone in a U-shape, which depends on the specific environmental conditions found in different solvents. We used molecular mechanics to illustrate conformations found by the NMR experiments. The measured redox potentials of MK-2 differed in three organic solvents, where MK-2 was most easily reduced in DMSO, which may suggest a combination of solvent effect (presumably in part because of differences in dielectric constants) and/or conformational differences of MK-2 in different organic solvents. Furthermore, MK-2 was found to associate with the interface of model membranes represented by Langmuir phospholipid monolayers and Aerosol-OT (AOT) reverse micelles. MK-2 adopts a slightly different U-shaped conformation within reverse micelles compared to within solution, which is in sharp contrast to the extended conformations illustrated in literature for MKs.
NAPHTHOQUINONE-BASED CHALCONE DERIVATIVES AND USES THEREOF
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Paragraph 00175, (2021/09/04)
The present disclosure provides compounds of formula 1 to inhibit or prevent mitochondrial dysfunction by augmenting mitochondrial function. Mitochondrial dysfunction is the hallmark of a wide range of diseases and disorders. Mitochondria are a promising therapeutic target for the detection, prevention and treatment of various human diseases such as cancer, neurodegenerative diseases, ischemia-reperfusion injury, diabetes and obesity.
Quinone Reduction by Organo-Osmium Half-Sandwich Transfer Hydrogenation Catalysts
Bolitho, Elizabeth M.,Coverdale, James P. C.,Sadler, Peter J.,Schünemann, Volker,Wolny, Juliusz A.,Worby, Nathan G.
, p. 3012 - 3023 (2021/09/13)
Organo-osmium(II) 16-electron complexes [OsII(η6-arene)(R-PhDPEN)] (where η6-arene =para-cymene or biphenyl) can catalyze the reduction of prochiral ketones to optically pure alcohols in the presence of a hydride source. Such complexes can achieve the conversion of pyruvate to unnatural http://www.w3.org/1999/xlinkd-lactate in cancer cells. To improve the catalytic performance of these osmium complexes, we have introduced electron-donor and electron-acceptor substituents (R) into thepara(R1) ormeta(R2) positions of the chiral R-phenyl-sulfonyl-diphenylethylenediamine (R-PhDPEN) ligands and explored the reduction of quinones, potential biological substrates, which play a major role in cellular electron transfer chains. We show that the series of [OsII(η6-arene)(R-PhDPEN)] derivatives exhibit high turnover frequencies, enantioselectivities (>92%), and conversions (>93%) for the asymmetric transfer hydrogenation (ATH) of acetophenone-derived substrates and reduce duroquinone and menadione to their di-alcohol derivatives. Modeling of the catalysis using density functional theory (DFT) calculations suggests a mechanism involving formic acid deprotonation assisted by the catalyst amine groups, phenyl-duroquinone stacking, hydride transfer to OsII, possible CO2coordination, and tilting of the η6-arene ring, followed by hydride transfer to the quinone. These findings not only reveal subtle differences between Ru(II) and Os(II) catalysts, but also introduce potential biological applications.
Stereoselective [4+2] cycloaddition of singlet oxygen to naphthalenes controlled by carbohydrates
Bauch, Marcel,Fudickar, Werner,Linker, Torsten
, (2021/06/12)
Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form.
