3840-30-0Relevant academic research and scientific papers
Anti-acute myeloid leukemia activity of 2-chloro-3-alkyl-1,4-naphthoquinone derivatives through inducing mtDNA damage and GSH depletion
Li, Kun,Yang, Kun,Zheng, Lifang,Li, Yuanyuan,Wang, Qi,Lin, Ruili,He, Dian
, p. 4191 - 4200 (2018/07/21)
2-Chloro-3-alkyl-1,4-naphthoquinone derivatives were synthesized and tested as the anti-acute myeloid leukaemia agents. The compound 9b (2-chloro-3-ethyl-5,6,7-trimethoxy-1,4-naphthoquinone) was the most potent toward HL-60 leukaemia cells. In mechanistic study for 9b, the protein levels of mtDNA-specific DNA polymerase γ (poly-γ) and mtDNA transcription factor A (mt-TFA) were decreased after the 24 h treatment, showing the occurrence of mtDNA damage. And 9b triggered cell cycle arrest at S phase accompanied by a secondary block in G2/M phase which had a direct link to the process of mtDNA damage. The dissipations of mitochondrial membrane potential and ATP also proceeded. On the other hand, 9b promoted the generation of ROS and resulted in the oxidation of intracellular GSH to GSSG. This process was coupled to the formation of adduct between 9b and GSH, detected by the UV–Vis spectrum and HRMS analysis. Depletion of GSH by buthionine sulfoximine enhanced ROS level and produced higher cytotoxicity, suggesting GSH was involved in the anti-leukemic mechanism of 9b. Together, our results provide new insights on the molecular mechanism of the derivatives of 2-chloro-1,4-naphthoquinone and 9b might be useful for the further development into an anti-leukemia agent.
Visible-Light-Mediated Iminyl Radical Generation from Benzyl Oxime Ether: Synthesis of Pyrroline via Hydroimination Cyclization
Usami, Kaoru,Yamaguchi, Eiji,Tada, Norihiro,Itoh, Akichika
supporting information, p. 5714 - 5717 (2018/09/21)
The treatment of an O-(4-methoxybenzyl) oxime ether bearing an olefin substituent and 1-chloroanthraquinone (1-Cl-AQN) catalyst in 2-butanone under visible-light irradiation affords pyrroline via an iminyl radical intramolecular hydroimination. Mechanistic studies indicate that iminyl radical generation mainly proceeds by hydrogen abstraction of the photocatalyst from the benzyl position of the oxime. Moreover, the hydrogen atom was identified in circulation from the benzylic position of the substrates between AQN and 2-butanone to quench the carbon radical without requiring any additional reagents.
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.
Activity of resveratrol triesters against primary acute lymphoblastic leukemia cells
Urbaniak, Alicja,Delgado, Magdalena,Kacprzak, Karol,Chambers, Timothy C.
, p. 2766 - 2770 (2017/05/29)
Resveratrol is a common polyphenol of plant origin known for its cancer prevention and other properties. Its wider application is limited due to poor water solubility, low stability, and weak bioavailability. To overcome these limitations, a series of 13 novel resveratrol triesters were synthesized previously. In this paper, we describe the synthesis of 3 additional derivatives and the activity of all 16 against primary acute lymphoblastic leukemia cells. Of these, 3 compounds were more potent than resveratrol (IC50?=?10.5?μM) namely: resveratryl triacetate (IC50?=?3.4?μM), resveratryl triisobutyrate (IC50?=?5.1?μM), and resveratryl triisovalerate (IC50?=?4.9?μM); all other derivatives had IC50 values of >10?μM. Further studies indicated that the active compounds caused G1 phase arrest, increased expression of p53, and induced characteristics of apoptotic cell death. Moreover, the compounds were only effective in cycling cells, with cells arrested in G1 phase being refractory.
AN EFFICIENT PROCESS FOR THE SYNTHESIS OF ALKOXY SUBSTITUTED BENZALDEHYDES
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Page/Page column 21; 22, (2016/07/27)
The present invention relates to the synthesis of alkoxy substituted benzaldehydes obtained from the corresponding alkoxy substituted benzenes. Alkoxy substituted benzaldehydes are products of broad commercial interest and are used as end products and intermediates in flavor and fragrance applications and pharmaceutical ingredients. For example, 3,4-methylendioxybenzaldehyde (also known as heliotropin or piperonal) is used widely both as a end product and intermediate for the above mentioned applications. Other examples include 3,4-dimethoxybenzaldehyde, 3,4,5- trimethoxybenzaldehyde and 3,4-ethylenedioxybenzene which are intermediates in the synthesis of active pharmaceutical intermediates.
New derivatives of 3,4-dihydroisoquinoline-3-carboxylic acid with free-radical scavenging, d-amino acid oxidase, acetylcholinesterase and butyrylcholinesterase inhibitory activity
Solecka, Jolanta,Guspiel, Adam,Postek, Magdalena,Ziemska, Joanna,Kawcki, Robert,Lczycka, Katarzyna,Osior, Agnieszka,Pietrzak, Bartlomiej,Pypowski, Krzysztof,Wyrzykowska, Agata
, p. 15866 - 15890 (2015/01/08)
A series of 3,4-dihydroisoquinoline-3-carboxylic acid derivatives were synthesised and tested for their free-radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH?), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS?+), superoxide anion radical (O2-) and nitric oxide radical (?NO) assays. We also studied D-amino acid oxidase (DAAO), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Almost each of newly synthesised compounds exhibited radical scavenging capabilities. Moreover, several compounds showed moderate inhibitory activities against DAAO, AChE and BuChE. Compounds with significant free-radical scavenging activity may be potential candidates for therapeutics used in oxidative-stress-related diseases.
Synthesis of salidroside analogues and their ability of DPPH radical scavenging activity
Zheng, Cheng,Guo, Yibing,Meng, Ying,Dou, Sufeng,Shao, Jian,Yang, Yumin
, p. 654 - 664 (2013/07/11)
Salidroside is a phenylpropanoid glycoside isolated from Rhodiolarosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, about 22 novel glycosides have been synthesized and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenge activity of each glycoside has been evaluated. 2-(3,4,5-Trihydroxyphenyl)ethyl β-D-galactopyranoside and 3-(3,4,5-trihydroxyphenyl)propyl β-D-glucopyranoside exhibit significant activity prior to salidroside and Vitamin C with EC50 values of 35.85 μM and 36.71 μM, respectively. The results indicate that the phenolic hydroxyl group of these compounds is important for radical scavenging activity and phenyl ring substitution by electron-donating substituents lead to increased antioxidant activity.
Novel hybrids from lamellarin D and combretastatin A 4 as cytotoxic agents
Shen, Li,Yang, Xiaochun,Yang, Bo,He, Qiaojun,Hu, Yongzhou
scheme or table, p. 11 - 18 (2010/03/03)
A new series of hybrids of lamellarin D and combretastatin A 4, 1,2-diphenyl-5,6-dihydropyrrolo [2,1-a] isoquinolines, were designed as cytotoxic agents based on principles of combination in medicinal chemistry and taking the parent compounds' different anti-proliferative mechanisms into consideration. Twenty-two novel hybrids were synthesized through a convenient route, with a key step of core pyrrole formation and evaluated for their anti-proliferative activities in vitro against K-562, A-549, SMMC-7721, SGC-7901 and HCT-116 cancer cell lines. The results showed that some hybrids had good anti-proliferative activities in low IC50 ranges.
Synthesis and biological evaluation of 3,4-diaryl-5-aminoisoxazole derivatives
Liu, Tao,Dong, Xiaowu,Xue, Na,Wu, Rui,He, Qiaojun,Yang, Bo,Hu, Yongzhou
scheme or table, p. 6279 - 6285 (2011/02/24)
A series of cis-restricted 3,4-diaryl-5-aminoisoxazoles have been synthesized and evaluated for their biological activities. Among them, compound 11a and 13a displayed potent cytotoxic activities in vitro against five human cancer cell lines with IC50 values in the low micromolar range and two compounds inhibited tubulin polymerization with IC50 value of 1.8, and 2.1 μM, respectively, similar to that of CA-4. Compound 13a could arrest at the G2/M phase of the cell cycle at the concentration of 0.1 and 1.0 μM and induce apoptosis at 0.1-1.0 μM.
Expanding the structural diversity of self-assembling dendrons and supramolecular dendrimers via complex building blocks
Percec, Virgil,Won, Betty C.,Peterca, Mihai,Heiney, Paul A.
, p. 11265 - 11278 (2008/03/14)
The design and synthesis of the first examples of AB4 and AB5 dendritic building blocks with complex architecture are reported. Structural and retrostructural analysis of supramolecular dendrimers self-assembled from hybrid dendrons based on different combinations of AB 4 and AB5 building blocks with AB2 and AB 3 benzyl ether dendrons demonstrated that none of these new hybrid dendrons exhibit the previously encountered conformations of libraries of benzyl ether dendrons. These hybrid dendrons enabled the discovery of some highly unusual tapered and conical dendrons generated by the intramolecular backfolding of their repeat units and of their apex. The new back-folded tapered dendrons have double thickness and self-assemble into pine-tree-like columns exhibiting a long-range 7/2 helical order. The back-folded conical dendrons self-assemble into spherical dendrimers. Non-back-folded truncated conical dendrons were also discovered. They self-assemble into spherical dendrimers with a less densely packed center. The discovery of dendrons displaying a novel crown-like conformation is also reported. Crown-like dendrons self-assemble into long-range 5/1 helical pyramidal columns. The long-range 7/2 and 5/1 helical structures were established by applying, for the first time, the helical diffraction theory to the analysis of X-ray patterns obtained from oriented fibers of supramolecular dendrimers.
