Preparation of cinnamic hydroxamic acid collector and study on flotation characteristics and mechanism of scheelite

In this paper,using methyl cinnamate as raw material,the new cinnamic hydroxamic acid collector(CIHA)was synthesized by the hydroxylamine method.The collector performance of hydroxamic acid was investigated for scheelite and gangue calcite,and the flotation separation test of scheelite and calcite was carried out with CIHA as the collector.The interaction mechanism between hydroxamic acid and scheelite minerals has also been investigated through zeta potential,Fourier transform infrared spectroscopy(FTIR)experiments,X-ray photoelectron spectroscopy(XPS)experiments,and density functional theory(DFT)calculation.The single mineral flotation test and artificially mixed ore showed that CIHA had an excellent collection effect and selectivity.Zeta potential,FTIR,and XPS showed that CIHA was adsorbed on the scheelite surface by strong chemical adsorption.The active group of CIHA was analyzed through quantum chemical calculation.It was speculated that C=O and N-O bonds could synthesize a five-membered chelated hydroxamic acid group with Ca element chelate on scheelite surface,changing hydrophobicity and making it more likely to emerge from the pulp.

Suberoylanilide hydroxamic acid upregulates reticulophagy receptor expression and promotes cell death in hepatocellular carcinoma cells

BACKGROUND Hepatocellular carcinoma(HCC)is a common clinical condition with a poor prognosis and few effective treatment options.Potent anticancer agents for treating HCC must be identified.Epigenetics plays an essential role in HCC tumorigenesis.Suberoylanilide hydroxamic acid(SAHA),the most common histone deacetylase inhibitor agent,triggers many forms of cell death in HCC.However,the underlying mechanism of action remains unclear.Family with sequence similarity 134 member B(FAM134B)-induced reticulophagy,a selective autophagic pathway,participates in the decision of cell fate and exhibits anticancer activity.This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death.AIM To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death.METHODS The viability,apoptosis,cell cycle,migration,and invasion of SAHA-treated Huh7 and MHCC97L cells were measured.Proteins related to the reticulophagy pathway,mitochondria-endoplasmic reticulum(ER)contact sites,intrinsic mitochondrial apoptosis,and histone acetylation were quantified using western blotting.ER and lysosome colocalization,and mitochondrial Ca^(2+)levels were characterized via confocal microscopy.The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization.Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region.RESULTS After SAHA treatment,the proliferation of Huh7 and MHCC97L cells was significantly inhibited,and the migration and invasion abilities were greatly blocked in vitro.This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner.Following treatment with SAHA,ER-phagy was activated,thereby triggering autophagy-mediated cell death of HCC cells in vitro.Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B promoter region.Further,SAHA disturbed the Ca^(2+)homeostasis and upregulated the level of autocrine motility factor receptor and proteins related to mitochondria-endoplasmic reticulum contact sites in HCC cells.Additionally,SAHA decreased the mitochondrial membrane potential levels,thereby accelerating the activation of the reticulophagy-mediated mitochondrial apoptosis pathway and promoting HCC cell death in vitro.CONCLUSION SAHA stimulates FAM134B-mediated ER-phagy to synergistically enhance the mitochondrial apoptotic pathway,thereby enhancing HCC cell death.

Histone deacetylase inhibitor suberoylanilide hydroxamic acid alleviates liver fibrosis by suppressing the transforming growth factor-β1 signal pathway

Background: Histone deacetylases(HDACs) inhibitors are new anti-fibrotic drugs that inhibit the activity of hepatic stellate cells. The present study focused on the anti-fibrotic function of HDAC inhibitor suberoylanilide hydroxamic acid(SAHA) by suppressing transforming growth factor-β1(TGF-β1) signaling. Methods: Male Sprague-Dawley rats were used to induce liver fibrosis with carbon tetrachloride(CCl 4) and LX2 cell(human hepatic stellate cell line) was stimulated by TGF-β1. Both animals and cells were treated with SAHA. The Smad7 and connective tissue growth factor(CTGF) mRNA levels were detected by real-time polymerase chain reaction(PCR). Western blotting was used to examine the protein levels of CTGF, Histone H3(H3), Smad7, Smad2/3, Acetyl-Histone H3(AH3), HDAC2, α-smooth muscle actin( α-SMA), HDAC6, p-Smad2/3 and HDAC8. In addition, the TGF-β1 and liver enzyme levels from rat serum were detected. Histopathological changes were examined by hematoxylin and eosin(HE), Sirius red and Masson trichrome staining. The α-SMA expression was detected by immumohistochemical staining. Results: Compared with control group, the TGF-β1 and liver enzyme levels from rat serum, together with the mRNA levels of CTGF and protein levels of CTGF, HDAC2, α-SMA, HDAC6, p-Smad2/3 and HDAC8 were elevated in fibrotic rats( P < 0.01). But the Smad7 mRNA and AH3 protein levels were notably suppressed in the fibrotic rats( P < 0.01). Pathological examination showed the typical changes of liver fibrosis in the fibrotic rats. After the treatment with SAHA, the levels of liver enzymes, TGF-β1, CTGF, HDAC2, α-SMA, HDAC6, p-Smad2/3 and HDAC8 were reduced( P < 0.01) and Smad7 and AH3 protein contents were elevated in liver fibrotic rats( P < 0.01). Moreover, immumohistochemistry showed that SAHA significantly suppressed the α-SMA protein content in fibrotic liver( P < 0.01). Conclusion: The HDAC inhibitor SAHA alleviated liver fibrosis by suppressing the TGF-β1 signaling.

Studies of benzyl hydroxamic acid/calcium lignosulphonate addition order in the flotation separation of smithsonite from calcite

Flotation separation of smithsonite from calcite is difficult due to their similar surface properties.In the present study,a reagent scheme of depressant calcium lignosulphonate(CLS) and collector benzyl hydroxamic acid(BHA) was introduced in the flotation of smithsonite from calcite.Microflotation tests revealed that the efficient flotation of smithsonite from calcite could only be obtained with the addition order of BHA before CLS,which was opposite to the widely-used order that adding depressant prior to the collector.The zeta potential measurements indicated that BHA selectively adsorbed onto smithsonite surface,then not allowed the CLS adsorption onto the smithsonite surface rather than calcite surface because of the steric hindrance,thereby the smithsonite surface remained hydrophobic while calcite surface became more hydrophilic after the addition of CLS.As a result,the calcite flotation was completely depressed while the smithsonite flotation recovery was still in high value,leading to the optimal flotation separation performance.

Synthesis and spectroscopic characterization of fluorescent solid rare-earth complexes with hydroxamic acids

The complexes RE_2(DHYA)_3 centre dot nH_2O in the title bar were synthesizedthrough some reactions of trivalent rare-earth ions. In the process of synthesis, dihydroxamicacids were taken as ligands while the alcohol was taken as a solvent. The ligands includedadipylhydroxamic acid (ADHA), p-phthalichydroxamic acid (PPHA), oxalohydroxamic acid (OXHA),butadihydroxamic acid (BDHA), o-phthalichydroxamic acid (OPHA), benzoylhydroxamic acid (BHA), etc.Measured at 25 deg C, the molar conductances in various modes are 13.00-21.05 S centre dot cm^2centre dot mol^(-1), which shows that rare-earth complexes are nonelectrolytes and the hydroxaminogroups of the complexes have taken part in bonding. Infrared spectra, ultraviolet spectra, nuclearmagnetic resonance (~1HNMR) spectra, and fluorescence spectra were used to investigate thecomplexes. Experiments have proved that the complexes of En^(3+)and Tb^(3+) with aromatic hydroxamicacids have good fluorescent characteristics.

Synthesis of a Novel Chiral Trihydroxamic Acid Containing L-Pro-L-Ala-L-Ala-β-(HO)Ala-OMe Unit

An N-hydroxyl peptide unit of H-L-Pro-L-Ala-L-Ala-β-（BnO）Ala-OMe was synthesized by stepwise chain building method in solution. Then, based on nitrilotriacetic acid backbone and this N-hydroxyl peptide unit, a novel chiral tripodal ligand P as an analogue of desferrichrome, has been synthesized. In neutral pH, ligand P formed stable tri（hydroxamato）- iron（Ⅲ） complexes which showed a maximum absorptiota （∑max=2750 M^-lcm^-1） at 422 nm in UV-Vis spectra. The characteristic absorption spectra are similar to those of natural trihydroxamate-type siderophores.

Synthesis and Crystal Structure of 2,2'-Dihydroxy-[1,1']binaphthalenyl-3,3'-bis-hydroxamic Acids

The first synthesis and structural characterization by X-ray crystallography of racemic 2,2＇-dihydroxy-[1,1＇]binaphthalenyl-3,3＇-bis-hydroxamic acids were reported.The com-pound（C28H30N4O8,Mr = 550.56） crystallizes in orthorhombic system,Fdd2 space group with a = 13.055（3）,b = 34.871（7）,c = 12.570（3） ,V = 5722（2） 3,Z = 8,Dc = 1.278 g/cm3,λ = 0.71073 ,μ（MoKα） = 0.095 mm-1,F（000） = 2320,S = 1.021,R = 0.0349 and wR = 0.0802 for 1757 observed reflections with I 〉 2σ（I）.The N-H and O atom are involved in two-dimensional intermolecular hydrogen bond nets,which further stabilize the structure.

Syntheses, Structures, and Luminescent Properties of the ZnⅡ and CdⅡ 1-D Chain Polymers Assembled by Salicylhydroxamic Acid

TWO complexes of compositions [Zn（H2shi）（CHsCOO）]. （1） and [Cd（H2shih（H20）]. （2） （H3shi = salicylhydroxamic acid） have been prepared under solvothermal conditions. They are characterized by X-ray single-crystal diffraction, IR and elemental analysis. The crystal of 1 belongs to the tetragonal system, space group I41/a with a = 18.972（3）, b = 18.972（3）, c = 10.938（2） A, V= 3937.1（I） A3, C9H9NOsZn, Mr - 276.54, Z = 16, Dc = 1.866 g/cm3,μ = 2.500 mm-1, F（000） = 2240, the final R = 0.0425 and wR = 0.123. The crystal of 2 belongs to the monoclinic system, space group P2/c with a = 16.647（3）, b = 6.4577（I）, c = 6.5623（I） A, V = 702.4（2） A3, C14H4Cd2N2OT, Mr = 434.68, Z = 2, Dc = 2.055 g/cm3,μ = 1.599 mm-1, F（000） = 432, the final R = 0.0211 and wR = 0.0761. They both possess I-D polymeric chain structures. The luminescent properties of complexes I and 2 have been investigated.

Flotation behavior and mechanism of rutile with nonyl hydroxamic acid

The flotation and surface interaction of rutile with nonyl hydroxamic acid were investigated in this work. The results show that the adsorption density and flotation recovery of rutile have similar tendency, especially the maximum recovery and adsorption occur at pH about 7.5. In terms of Fourier transform infrared（FTIR） spectroscopic analysis, chemical adsorption is identified on the surface of rutile, where a chelate of O,O-five-membered rings with Ti^4＋ on the surface of rutile may form. Adsorption measurements, Zeta potential test, IR spectrum analyses, and solution chemistry calculations illustrate that the adsorption on the rutile surface involves both physical and chemical adsorption, while chemical adsorption is dominant.

Oxoarylation of ynamides with N-aryl hydroxamic acids

Ynamides are electron-rich alkynes with unique reactivities and act as flexible building blocks in organic synthesis.Therefore,the investigation for transformation of ynamides with exceptional selectivity and efficiency is attractive and interesting.Herein,we report an oxoarylation of ynamides with N-aryl hydroxamic acids.In the presence of catalytic Cu(OTf)_(2),both the terminal and internal ynamides could undergo an addition/[3,3] sigmatropic rearrangement cascade with N-aryl hydroxamic acids to achieve oxoarylation,along with providing selective entry to(ortho-amino)arylacetamides and oxindoles.Moreover,deuterium-labelling reaction and gram-scale reaction were conducted to probe the mechanism and showcase the scalability.

Synthesis,O_2-binding ability and catalytic oxidation performance of cobalt(Ⅱ) complexes with dihydroxamic acid functionalized N-pivot lariat ethers

Novel Co（Ⅱ） complexes with dihydroxamic acids functionalized N-pivot lariat ether CoL^1-CoL^4 were synthesized and characterized.Their oxygenation constants（ln K_（O2）） and thermodynamic parameters（△H°,△S°） were measured.And their catalytic performance in oxidation of p-xylene to p-toluic acid（PTA） was investigated.The enhancement of O_2-binding and catalytic oxidation activity by the oxa aza crown ether ring of the cobalt complexes were discussed.

A Simple Method for the Isolation and Purification of 2,4-Dihydroxy-7-Methoxy-2H-1,4-Benzoxazin-3(4H)-One (DIMBOA) from Maize (Zea mays L.) Seedlings

2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3（4H）-one （DIMBOA）, the dominant benzoxazinoid hydroxamic acid in maize （Zea Mays L.）, serves as important factors of resistance against insects and microbial diseases, allelochemicals used in competition with other plants. In this paper, a novel and simple method for the isolation and purification of DIMBOA from maize seedlings was developed. Frozen shoots from 7-d-old maize seedlings （1 000×g） were firstly defrosted and then were directly homogenized and extracted with ethyl acetate. The macerate was allowed to stand at room temperature （25±2）°C for 1 h to allow enzymatic release of DIMBOA from DIMBOA-glucoside. Then the ethyl acetate phase was filtered, dried and evaporated to dryness. The resulting light-tan, semicrystalline residue was stored at -20°C for 24 h. Upon recrystallization from acetone-hexane, a relative higher yield （0.58 g） of pure DIMBOA crystals was obtained compared with the yield afforded by Woodward methodology （0.26 g）.

Histone Deacetylase Inhibitor SAHA Induces Expression of Fatty Acid-Binding Protein 4 and Inhibits Replication of Human Cytomegalovirus

Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to its anticancer activity,SAHA has significant effects on the growth of many viruses. The effect of SAHA on replication of human cytomegalovirus(HCMV) has not, however, been investigated. Here, we showed that the replication of HCMV was significantly suppressed by treatment with SAHA at concentrations that did not show appreciable cytotoxicity. SAHA reduced transcription and protein levels of HCMV immediate early genes, showing that SAHA acts at an early stage in the viral life-cycle. RNAsequencing data mining showed that numerous pathways and molecules were affected by SAHA. Interferon-mediated immunity was one of the most relevant pathways in the RNA-sequencing data, and we confirmed that SAHA inhibits HCMV-induced IFN-mediated immune responses using quantitative Real-time PCR(qRT-PCR). Fatty acid-binding protein 4(FABP4), which plays a role in lipid metabolism, was identified by RNA-sequencing. We found that FABP4 expression was reduced by HCMV infection but increased by treatment with SAHA. We then showed that knockdown of FABP4 partially rescued the effect of SAHA on HCMV replication. Our data suggest that FABP4 contributes to the inhibitory effect of SAHA on HCMV replication.

Potential therapeutic effect of epigenetic therapy on Ireatment-induced neuroendocrine prostate cancer

Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model （LNCaP/NE1.8） to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.

Synthesis, Characterization and in vitro Antitumour Activity of the Di-n-butyltin(IV) Complexes of Some Arylhydroxamates

Fourteen new di n butyltin(IV) complexes of hydroxamic acids of the formula Bu 2 SnL 2 (HL=hydroxamic acids) were synthesized by the reaction of Bu 2 SnO and hydroxamic acids in dry toluene and ethanol media. The compounds were characterized by elemental analyses, molecular weight, IR and 1 H NMR spectroscopy. The results indicate that n Bu 2 SnL 2 have distorted trans octahedral structure. The antitumor activity in vitro against human A 549 tumor cells and P388 leukemia was presented, and their structure activity relationship was discussed.