Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells.

Malignant melanoma represents a form of skin cancer characterized by a bleak prognosis and heightened resistance to traditional therapies. Quercetin has demonstrated notable anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects across various cancer types. However, the intricate relationship between quercetin's anti-cancer properties and ganglioside expression in melanoma remains incompletely understood. In this study, quercetin manifests specific anti-proliferative, anti-migratory, and cell-cycle arrest effects, inducing mitochondrial dysfunction and apoptosis in two melanoma cancer cell lines. This positions quercetin as a promising candidate for treating malignant melanoma. Moreover, our investigation indicates that quercetin significantly reduces the expression levels of ganglioside GD3 and its synthetic enzyme. Notably, this reduction is achieved through the inhibition of the FAK/paxillin/Akt signaling pathway, which plays a crucial role in cancer development. Taken together, our findings suggest that quercetin may be a potent anti-cancer drug candidate for the treatment of malignant melanoma.

7,8-Dihydroxyflavone induces mitochondrial apoptosis and down-regulates the expression of ganglioside GD3 in malignant melanoma cells.

Malignant melanoma is a skin cancer with poor prognosis and high resistance to conventional treatment. 7,8-dihydroxyflavone (7,8-DHF) has shown anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects in several types of cancer. However, the relationship between ganglioside expression and the anti-cancer effects of 7,8-DHF in melanoma is not fully understood. In the present study, 7,8-DHF exhibits specific anti-proliferation, anti-migration, and G2/M phase cell-cycle arrest effects on both melanoma cancer cell lines, and induces mitochondrial dysfunction and apoptosis, making it a potent candidate for anti-melanoma treatment. Furthermore, we confirmed that 7,8-DHF significantly reduces the expression levels of ganglioside GD3 and its synthase, which are known to be closely involved in carcinogenesis. Taken together, our findings suggest that 7,8-DHF may be a potent anti-cancer drug candidate for the treatment of malignant melanoma.

An anti-clogging method for improving the performance and lifespan of blood plasma separation devices in real-time and continuous microfluidic systems.

On-chip blood plasma separators using microfluidic channels are typically developed as disposable devices for short-term use only because blood cells tend to clog the microchannels, limiting their application in real-time and continuous systems. In this study, we propose an anti-clogging method. We applied dielectrophoresis to prevent microchannel clogging in a plasma separator that can be used over long periods for real-time and continuous monitoring. Prior to applying the anti-clogging method, the blood plasma separator stopped working after 4 h. In contrast, by manipulating the separator with the new anti-clogging method at a voltage of 20 V, it continued working in a long-term experiment for 12 h without performance deterioration or an increase in cell loss. Two critical performance parameters of the manipulated separator, the purity efficiency and the plasma yield, were 97.23 ± 5.43% and 38.95 ± 9.34%, respectively, at 20 V after 15 min. Interestingly, the two performance parameters did not decrease during the long-term experiment. Hence, the blood plasma separator with the anti-clogging method is an interesting device for use in real-time and continuous blood plasma separation systems because of its consistent performance and improved lifespan.

Particle size spectrometer using inertial classification and electrical measurement techniques for real-time monitoring of particle size distribution.

To achieve real-time monitoring of aerodynamic submicron particle size distributions at a point-of-interest, we developed a high-performance particle size spectrometer that is compact, low-cost, and portable. The present system consists of four key components: a unipolar mini-discharger for electrically charging particles, an inertial size-separator for classifying charged particles into five size fractions in terms of their aerodynamic sizes, a portable multi-channel electrometer for detecting femto-ampere currents carried by charged particles at each stage, and a retrieval algorithm for converting the current data into a smooth particle size distribution. The unipolar mini-discharger and inertial size separator were quantitatively characterised by using standard polystyrene latex (PSL) particles. The experimentally determined cut-off diameters at each stage in the inertial size separator were 1.17, 0.94, 0.71, 0.54, and 0.23 µm, respectively. Then, the system was compared with a commercial reference aerodynamic particle sizer (APS) in the environment where the number concentration and the average size of TiO2 particles were changing. The present system resolved peak size and geometric standard deviation of particles to within 11.2%, and 6.3%, respectively, indicating that the system can be used to accurately monitor submicron particle size distributions in real time.

Synthesis and cellular uptake properties of guanidine-containing molecular transporters built on the sucrose scaffold.

Novel sucrose-based G7 molecular transporters show different patterns of intracellular localization depending on the nature of the linker chains as well as the fluorescent dyes.

A convenient route to diverse heterocycles through an addition of beta-amino carbonyl compounds to 3-halogeno-4-methoxybenzynes.

[reaction: see text] 3-Halogeno-4-methoxybenzynes 5 generated from 5-(3-halogeno-4-methoxyphenyl)thianthrenium perchlorates 1 and LDA in THF at reflux reacted with various beta-amino carbonyl compounds and 2-aminophenyl benzenesulfonate etc. to give diverse heterocyclic compounds.

Synthesis, conformation, and complexation of novel 25,26,27,28- tetrahydroxy-5,11:17,23-bis[[2,2'-thioxydi(o-phenylene)dithioxy]- diphenylthio]calix[4]arene.

Calix[4]arenes 1a,b having an electron-donating group, i.e., OH and OMe, at the lower rim reacted with thianthrene cation radical perchlorate in CH3CN at room temperature to give the corresponding thianthrenium perchlorates 3a,b in excellent yields. Treatment of 3a,b comprising a mixture of conformational isomers with NaSH.xH2O in DMF at reflux afforded the sulfur-containing cyclized compounds 4a,b, respectively. Compound 4a having a cone conformation consisted of two conformational isomers in a ratio of 0.077:1. Temperature-dependent 1H NMR study in DMF showed that conformational isomerization between the two isomers occurred with energy barriers of 14.97 and 14.10 kcal/mol at 100 and 110 degrees C, respectively. The Jobs plot of 4a against Ag+ picrate indicated that compound 4a strongly produced a 1:2 complex with Ag+ ions. Molecular mechanics calculations indicated that the conformation of the energy-minimized 4a-2Ag+ picrate complex had two crushed pyramidal geometries made up of Ag+ ion and four sulfur atoms, i.e., S1, S2, S4, S5 and S6, S7, S9, S10, respectively.

Potassium hydroxide-mediated novel rearrangement of 2-alkyl-sulfonyl-2-arylsulfonyl-1-phenylethanones to 1-aryl-2-(arylsulfonylmethanesulfonyl)ethanones.

Treatment of a solution of a mixture of 1-aryl-2-arylsulfonylethanones 9 and alkylsulfonyl chlorides (1.5-2.0 equiv) in THF at 0 degree C with potassium hydroxide (8 equiv) for 10 min gave a rearrangement product, i.e., 1-aryl-2-(arylsulfonylmethanesulfonyl)ethanones 8, in excellent yields. Regiospecific methyl- and ethylation at the methylene carbon sandwiched between two sulfonyl groups of 8 could be achieved by the reactions of 7i-j with LDA (1 equiv) in THF at room temperature, respectively.

Facile synthesis of 4-alkyl (and aryl)-2-aryl-6-diazo-4h- thieno[3,2-b]pyridine-5,7-diones.

Treatment of 3-[3-alkyl (and aryl)amino-5-arylthieno-2-yl]-2-diazo-3-oxopropanoates 8 with TMSOTf (3 equiv) in the presence of Et(3)N (6 equiv) in CH(2)Cl(2) for 1 h at room temperature afforded 4-alkyl (and aryl)-2-aryl-6-diazo-4H-thieno[3,2-b]pyridine-5,7-diones 14 in excellent yields. On heating of 14 in the presence of a catalytic amount of Rh(2)(CF(3)CF(2)CF(2)CO(2))(4) in PhH for 4-10 h at reflux, corresponding ring contraction products, 4-alkyl (and aryl)-5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-ones 16, were produced in good to excellent yields.

Novel synthesis and reactions of 5,7-dialkyl-4,6-dioxo-4,5,6,7-tetrahydro- isothiazolo[3,4,-d]pyrimidine-3-carbonitriles and 6-methyl-4-oxo-4H-1-aza-5-oxa-2- thiaindene-3-carbonitrile.

[reaction: see text] 5,7-Dialkyl-4,6-dioxo-4,5,6,7-tetrahydroisothiazolo[3,4-d]pyrimidine-3-carbonitriles 4, prepared from 6-amino-1,3-dialkyluracils 3 and 4,5-dichloro-5H-1,2,3-dithiazolium chloride (Appel's salt) 1, are utilized for the preparation of new derivatives of 4 bearing amino, alkylthio, amido, thioamido, tetrazolyl, and carboximidic acid ethyl ester groups at position 3. Similarly, the reactions of 6-methyl-4-oxo-4H-1-aza-5-oxa-2-thiaindene-3-carbonitrile 8, prepared from 4-amino-6-methyl-2-pyrone 6 and 1, with alkyl- and arylamines in DMF at 50 degrees C and reflux afforded different isothiazole derivatives 11 and 17, respectively. On the other hand, treatment of 8 with 1,3-diaminopropane in THF at room temperature, followed by chromatography on silica gel, gave 3-(2-oxopropyl)-6,7,8-trihydro-4H-1-thia-2,5,9-triazacyclopentacyclononene-4,10-dione 12 in 59% yield.

Novel synthesis of cis-nickel(II) 3-alkylimino-3-alkyl(or aryl)thio-1-arylpropenethiolates and their application to the preparation of 5-aryl-3-(arylthio)isothiazoles.

Treatment of (E)-3-alkylamino-3-alkylthio-1-(thioaroyl)propenes 2 with Ni(OAc)2.4H2O in EtOH at room temperature gave cis-Ni(II)-3-alkylimino-3-alkylthio-1-arylpropenethiolates 3 in excellent yields. Heating a mixture of 3 and alkyl- or arylthiols in 1,2-dichloroethane gave new ketene S,N-acetals 4 having new alkyl- or arylthio groups depending on the thiols employed. For the first time, 5-aryl-3-(arylthio)isothiazoles were prepared from 2 with an arylthio group according to a known procedure.

Novel synthesis of 5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-ones via the rhodium(II)-mediated wolff rearrangement of 3-(thieno-2-yl)-3-oxo-2-diazopropanoates.

[reaction: see text] Treatment of thioaryolketene S,N-acetals 12 with Hg(OAc)(2) followed by addition of 2-diazo-3-trimethylsilyloxy-3-butenoic acid alkyl esters 15 in CH(2)Cl(2) at room temperature gave 3-(3-alkylamino-5-arylthieno-2-yl)-3-oxo-2-diazopropanoates 16 in good yields. Subsequent reactions of 16 with a catalytic amount of Rh(2)(OAc)(4).2H(2)O in benzene at reflux afforded a mixture of 5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-ones 18 and the corresponding enols 19 in excellent yields.