Synthesis, Crystal Structure and Fungicidal Activity of N-(4-tert-buty)-5-(1,2,4-triazol-1-yl)thiazol-2-yl)propionamide

The title compound has been synthesized by the reaction of 4-tert-butyl-5-（1,2,4- triazol-1-yl）-2-aminothiazole with propionic anhydride, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to the orthorhombic system, space group Pbca with α = 18.441（2）, b = 8.3284（9）, c = 19.257（2） A, Z = 8, V = 2957.5（5） A3, Mr = 279.37, Dc = 1.255 mg/m3, S = 1.033, μ =0.219 mm^-1, F（000） = 1184, the final R = 0.0349 and wR = 0.0876 for 2629 observed reflections （I 〉 2σ（I））. X-ray crystal structure presents the intermolecular N–H···N hydrogen bond, which plays an important role in stabilizing the crystal structure. The preliminary bioassay indicates that the title compound exhibits potent fungicidal activity against R. Solani （25 mg/L） with inhibition rate of 80.0%.

Synthesis,Crystal Structure and Antitumor Activity of N-(4-tert-butyl-5-(4-chlorobenzyl)thiazol-2-yl)-2,6-difluorobenzamide

The title compound was synthesized by the reaction of 4-tert-butyl-5-（4-chlorobenzyl）-2-aminothiazole with 2,6-difluorobenzoic acid. The crystal structure of the title compound, C21H19ClF2N2OS, was determined by single-crystal X-ray diffraction. The crystal belongs to the triclinic system, space group Pbca with a = 12.6479（13）, b = 13.1204（13）, c = 14.1341（15）, Z = 4, V = 2011.5（4）3, Mr = 420.89, Dc = 1.390 g/cm3, S = 1.023, μ = 0.326 mm-1, F（000） = 872, the final R = 0.0365 and wR = 0.0880 for 6101 observed reflections（I 〉 2σ（I））, and R = 0.0507, wR = 0.0978 for 7779 independent reflections. X-ray crystal structure displays that the hydrogen bonding interactions observed link the molecules to form a dimeric unit. The preliminary biological test of the title compound shows good antitumor activity, with IC50 of 0.046 μmol/mL against the Hela cell line.

Synthesis and Crystal Structure of 3,3'-Bis(5-(N-(4-hydroxylphenyl)imidomethyl)- pyrrol-2-yl)pentane·2CH_3OH

3,3＇-Bis（5-（N-（4-hydroxylphenyl）imidomethyl）pyrrol-2-yl）pentane 1 has been synthesized and characterized. The crystal of its methanol complex, 1·（CH3OH）2, belongs to the orthorhombic system, space group Pccn with a = 18.094（2）, b = 11.6890（16）, c = 13.3629（19） , V = 2826.3（7） 3, Z = 8, C14.5H18N2O2, Mr = 252.31, Dc = 1.186 g/cm3, F（000） = 1080 and μ（MoKα） = 0.080 mm-1. The final R = 0.0662 and wR = 0.1801 for 1908 observed reflections with I 2σ（I）, and R = 0.0800 and wR = 0.1948 for all reflections. In the solid state, bridged by included methanol molecules, the molecules of compound 1 form interpenetrated grid structure through N–H···O and O–H···O hydrogen bonds.

Synthesis, Crystal Structure and Antitumor Activities of N-(2-(1H-indol-3-yl)ethyl)-2-nitroaniline

The title compound, N-(2-(1H-indol-3-yl)ethyl)-2-nitroaniline(C16H15N3O2, Mr = 281.31), has been synthesized by the multicomponent reaction of milder Ullmann, and its structure was characterized by 1H NMR, 13 C NMR, IR, H RMS(ESI) and single-crystal X-ray diffraction. It crystallizes in monoclinic, space group I2/c with a = 15.0212(10), b = 9.4911(6), c = 20.3075(13) A, β = 100.776(7)o, V = 2844.1(3)A3, Z = 8, Dc = 1.314 g/cm3, F(000) = 1184.0, μ = 0.089 mm-1, the final R = 0.0574 and w R = 0.1688 for 1701 observed reflections(I 】 2σ(I)). X-ray analysis indicates three major N(2)–H(2)···O(2), C(13)–H(13)···O(2), N(2)–H(2)···N(3) hydrogen bonds and π-π stacking interactions in the crystal structure. The preliminary biological test shows that the title compound has a good antitumor activity against A549 in vitro with the IC50 value of 35 μmol/L.

Synthesis and Crystal Structure of N-((6-chloropyridin-3-yl)methyl)-6-ethoxy-N-ethyl-3-nitropyridin-2-amine

The title compound N-（（6-chloropyridin-3-yl）methyl）-6-ethoxy-N-ethyl-3-nitropyri-din-2-amine（4） was synthesized by reacting the mixture of 6-chloro-2-ethoxy-3-nitropyridine（1） and 2-chloro-6-ethoxy-3-nitropyridine（2） with 3,and its structure was determined by X-ray single-crystal diffraction.The crystal belongs to the monoclinic system,space group P21/n with a = 7.3441（2）,b = 9.9041（3）,c = 11.7368（3） ,α = 101.410（2）,β = 102.1340（10）,γ = 99.594（2）o,μ = 0.260 mm^-1,Mr = 336.78,V = 798.58（4）（A°）^3,Z = 2,Dc = 1.401g/cm^3,F（000） = 352,T = 296（2） K,R = 0.0210 and wR = 0.1053.

Synthesis and Crystal Structure of N-[(3aR,4R,4aR,5aS,6S,6aS)-1,3-Dioxooctahydro-4,6-ethenocyclopropa[f]isoindol-2(1H)-yl]-3-(trifluoromethyl)phenylmethanimine

The crystal structure of the title compound（C19H15F3N2O2,Mr = 360.33） was determined by single-crystal X-ray diffraction.The crystal belongs to triclinic,space group P1,with a = 6.5604（7）,b = 13.9614（16）,c = 18.1790（18） ,α = 102.749（7）,β = 97.542（6）,γ = 94.355（4）°,V = 1600.5（3） 3,Z = 4,Dc = 1.495 g/cm3,λ（MoKα） = 0.71070,F（000） = 744,μ（MoKα） = 0.122 mm-1,R = 0.0434 and wR = 0.1051.A total of 7590 unique reflections were collected,of which 5429 with ｜F｜2 ≥ 2σ｜F｜2 were observed.The two cyclohexene rings in the molecule adopt boat-boat conformations with the deviations of ring atoms C（9） and C10 from the C（5）/C（6）/C（7）/C（8） plane（Ⅰ） by 1.1204（0.0023） and 1.1132（0.0023） ,respectively,whereas from the C（2）/C（3）/C（5）/C（8） plane（Ⅱ） by 1.1627（0.0022） and 1.1818（0.0021） ,respectively.In the cyclopropane and lactam rings,atoms C（11） and N（1） point towards the double bond of C（9）-C（10） and the dihedral angle between the ring plane（Ⅲ） containing C（1）,C（2）,C（3） and C（4） and plane（IV） consisting of C（6）,C（7） and C（11） is 55.76（0.07）°.The dihedral angles between planes Ⅳ and Ⅰ and Ⅱ and Ⅲare 63.58（0.07）° and 58.10（0.06）°,respectively.The dihedral angle between the benzene ring C（13）～ C（18） and plane Ⅳ is 42.41（0.06）°.

Studies on the esterifications of 9-(hydroxyimino)-4-methyl-8,9-dihydrofuro[2,3-h]chromen-2-one with acid chlorides under different conditions

The esterifications of 9-（hydroxyimino）-4-methyl-8,9-dihydrofuro[2,3-h]chromen-2-one （4） with acid chlorides afforded normal oxime-esters 3a-e in 35-78% yields in presence of excessive 4-dimethylaminopyridine as the acid scavenger, whereas the reactions gave unexpected 8-substituted products N-（8-chloro-4-methyl-2-oxo-2H-furo-[2,3-h]chromen-9-yl）amides （5a-c） and 4-methyl-2,9-dioxo-8,9-dihydro-2H-furo[2,3-h]chromen-8-ylcarboxyloates （6d-e） by using excessive acid chlorides. The structures of 10 new compounds were determined by 1H NMR, 13C NMR, MS and HRMS, and the possible mechanism for the formation of unexpected products 5a--c and 6d-e was also proposed.

Lipophilicity determination of N-( benzothiazol-2-yl )-α-amino alkyl phosphonic diesters by RP-HPLC and RP-HPTLC

Using methanol-water mixtures as the mobile phase, the chromatographic retention parameters k' and Rf were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and reversed-phase high-performance thin-layer chromatography (RP-HPTLC) for N-(benzothiazol-2-yl)-α-amino alkyl phosphoric diesters and the correlation with lipophilicity parameter (Clog P) was established. Log Kw values obtained from RP-HPLC and Rm values obtained from RP-HPTLC can be used to evaluate the lipophilicity of this kind of compounds. Chromatographic method is a good alternative for lipophilicity measurement.

Effect of protease inhibitor from Agaricus bisporus on glucose uptake and oxidative stress in 3T3-L1 adipocytes

Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.

Synthesis and Antibacterial Activities of N- [（1-Aryl-3-phenyl-pyrazol- 4-yl）methylene]-2-（halo-o-hydroxyphenyl）hydrazide Derivatives

A series of novel N-[（1-aryl-3-phenyl-pyrazol-4-yl）methylene]-2-（halo-o-hydroxyphenyl）hydrazide derivatives was synthesized and the antibacterial activity of each of them was evaluated. The supposed reaction mechanism of acquiring compounds 3a--3d is that catalytic activity is enhanced by the electron-donating groups of the first phenyl ring while decreased by electron-withdrawing groups of that ring. The result of preliminary bioassay shows that the lowest minimal inhibitory concentration（MIC） of the title compounds against Escherichia coli is 2 ℃g/mL. MIC values against Monilia albiean and Staphloeoeeus aureus are as low as 4 ~g/mL. They will be a series of potential antibacterial compounds against fungi and gram-negative bacteria.

Preparation,Crystal Structure and Fungicidal Activity of N-(5-(benzofuranol-7-oxymethyl)-1,3,4-thiadiazol-2-yl)amide Compounds

A variety of new N-(5-(benzofuranol-7-oxymethyl)-1,3,4-thiadiazol-2-yl)amide compounds(8a-i)were synthesized through four steps from benzofuranol as raw materials.The crystal structure of compound 8a(C17H21N3O3S,Mr=347.43)was measured by X-ray diffraction,which was classified as monoclinic system,Z=4,V=1742.72(8)Å3,Dc=1.324 Mg/m3,F(000)=736,S=1.03,μ=0.21 mm-1,space group P21 with a=9.9177(3),b=8.9519(2),c=19.8679(5)Å,the final R=0.035 and wR=0.105 for 3873 observed reflections(I>2σ(I)).The X-ray structure presented N(3)-H(3)···N(2)and C(6)-H(6)···O(3)intermolecular hydrogen bonds,which acted as an important role in stabilizing the crystal structure.Additionally,preliminary biological assay on compound 8a showed good fungicidal activity in vivo,with the inhibition of 75%against Pseudoperonospora cu-bensis at 200 mg/L.

AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer

Drastic surges in intracellular reactive oxygen species(ROS)induce cell apoptosis,while most chemotherapy drugs lead to the accumulation of ROS.Here,we constructed an organic compound,arsenical N-(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide(AAZ2),which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer(GC).Mechanistically,by targeting pyruvate dehydrogenase kinase 1(PDK1),AAZ2 caused metabolism alteration and the imbalance of redox homeostasis,followed by the inhibition of phosphoinositide-3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway and leading to the activation of B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)/caspase-9(Cas9)/Cas3 cascades.Importantly,our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft.Overall,our data suggested that AAZ2 could contribute to metabolic abnormalities,leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

Chaihushugan decoction exerts antiepileptic effects by increasing hippocampal glutamate metabolism in pentylenetetrazole-kindled rats

OBJECTIVE: To investigate the antiepileptic effects of Chaihushugan decoction(CHSGD) in rats with pentylenetetrazole(PTZ)-induced seizures and to discuss the impact of CHSGD on glutamate metabolism, a hypothesized underlying mechanism of seizure reduction.METHODS: Fifty Wistar rats were divided randomly into either control(n = 10) or experimental(n = 40)groups. Rats in the control group were administered physiological saline intraperitoneally. A subconvulsive dose of PTZ(35 mg/kg) was administered intraperitoneally to rats in the experimental group to induce seizures. The fully PTZ-kindled rats were then randomly divided into five subgroups(n = 8 each) based on the following treatment categories: physiological saline, VPA(200 mg/kg), CHSGD(2.5 g/kg), CHSGD(5 g/kg), or CHSGD(10 g/kg),administered orally once per day, respectively. On day 28 following initiation of drug treatment, seizures were monitored. The rats were then sacrificed, and hippocampal dissections were performed for subsequent studies.RESULTS: CHSGD significantly prolonged the latency of myoclonic, clonic, and tonic seizures, while decreasing overall seizure rates in the kindled rats.The measured concentrations of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose(2-NBDG) and glutamate were significantly lower in the hippocampi of kindled rats in groups treated with CHSGD compared with those treated with PTZ alone. In addition, CHSGD was found to up-regulate both the expression of glutamate transporter-1(GLT-1) protein and the activity of glutamine synthetase(GS) in the hippocampi of kindled rats.CONCLUSION: These results suggest that CHSGD has antiepileptic effects on PTZ-induced seizures.The results further suggest an increase in glutamate metabolism at the synaptic cleft is a putative underlying mechanism of seizure reduction.

Synthesis and biological evaluation of ^(99m)Tc-HEDTA/HYNIC-MPP4 complex for 5-HT_(1A) receptor imaging

5-HT_(1A)receptor is associated with a variety of pathophysiology of neuropsychiatric disorders.Accordingly,we have synthesized a new 5-HT_(1A) receptor ligand(HYNIC-MPP4)and labeled it with^(99m)Tc using N-(2-hydroxyethyl)ethylenediaminetriacetic acid(HEDTA)as coligand.^(99m)Tc-HEDTA/HYNIC-MPP4 was prepared under pH 6 at room temperature.Biodistribution of^(99m)Tc-HEDTA/HYNIC-MPP4 in normal mice showed that this complex had moderate brain uptake(0.60%ID·g^(-1)at 2 min p.i.)and good retention.The hippocampus had the highest radioactivity uptake at 2 min p.i.(1.84%ID·g^(-1)).The ratio of Hipp/CB was 3.1 at 2 min p.i.and increased to 4.4 at 60 min p.i.After blocking with 8-hydroxy-2-(dipropylamino)tetralin,the uptake of hippocampus was decreased significantly from 1.84%ID·g^(-1) to 0.53%ID·g^(-1) at 2 min p.i.,while the cerebellum had no significant decrease.This^(99m)Tc complex could be a potent agent for 5-HT_(1A) receptor imaging.