BACKGROUND: The nuclear translocation of transcription factors may be a critical factor in the intracellular pathway involved in ischemia/reperfusion(I/R) injury. The aim of the study was to evaluate the role of nucle...BACKGROUND: The nuclear translocation of transcription factors may be a critical factor in the intracellular pathway involved in ischemia/reperfusion(I/R) injury. The aim of the study was to evaluate the role of nuclear factor-kappa B (NF-κB) in the pathogenesis of liver injury induced by intestinal ischemia/reperfusion (IIR) and to investigate the effect of pyrrolidine dithiocarbamate (PDTC) on this liver injury. METHODS: Male Wistar rats were divided randomly into three experimental groups (8 rats in each): sham operation group (control group); intestinal/reperfusion group(I/R group): animals received 1-hour of intestinal ischemia and 2-hour reperfusion; and PDTC treatment group (PDTC group): animals that received I/R subject to PDTC treatment (100 mg/kg). The histological changes in the liver and intestine were observed, and the serum levels of tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver superoxide dismutase (SOD), and nitrite/nitrate (NO) were measured. The immunohistochemical expression and Western blot analysis of liver NF-κB and intercellular adhesion molecule-1(ICAM-1) were observed. RESULTS: IIR induced liver injury characterized by the histological changes of liver edema, hemorrhage, polymorphonuclear neutrophil (PMN) infiltration, and elevated serum levels of AST and ALT. The serum TNF-α level was significantly higher than that of the control group(P【0.01) and a high level of liver oxidant product was observed (P【0.01). These changes were parallel to the positive expression of NF-κB and ICAM-1. After the administration of PDTC, the histological changes after liver injury were improved; the levels of SOD and NO in the liver were elevated and reduced, respectively (P【0.01). The expressions of ICAM-1 and NF-κB in the liver were weakened (P【0.01). CONCLUSION: NF-κB plays an important role in the pathogenesis of liver injury induced by HR. PDTC, an agent known to inhibit the activation of NF-κB, can reduce and prevent this injury.展开更多
Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and r...Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.展开更多
Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were ora...Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine(500 mg/kg), pyrrolidine dithiocarbamate(100 mg/kg), and saxagliptin(10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase(MAPK), phosphorylated extracellular signal-regulated kinase(ERK), c AMP response element-binding protein(CREB), interleukin-12(IL-12), caspase-3, β-defensin, inducible nitric oxide synthase(i NOS) and glucagon like peptide-1(GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, i NOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and i NOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.展开更多
Studies have indicated that flavonoid luteolin is a potential inhibitor of tumor cell proliferation and may function as an anticarcinogenic agent. Pyrrolidine dithiocarbamate (PDTC), a synthetic compound, may exhibit ...Studies have indicated that flavonoid luteolin is a potential inhibitor of tumor cell proliferation and may function as an anticarcinogenic agent. Pyrrolidine dithiocarbamate (PDTC), a synthetic compound, may exhibit biphasic effects on apoptosis depending on the experimental context. Previously, we found that luteolin induced the activation of the proapoptotic proteins, such as Bad, Bid, and Bax, in HL-60 human leukemia cells. We also explored the modulatory effects and molecular mechanisms of PDTC on the cytotoxicity of luteolin in HL-60 cells;PDTC could interfere with luteolin’s ability to cleave poly(ADP-ribose)-polymerase (PARP) and DNA fragmentation of factor-45 (DFF-45). In the current study, we further investigated the effect of PDTC on the luteolin-induced death-receptor pathway and the cleavage of the Bcl-2 family members. We found that the combination of luteolin and PDTC increased the survival of the HL-60 cells such that PDTC inhibited both extrinsic and intrinsic pathways in luteolin-induced apoptosis.展开更多
N-Boc-2, 5-bis(trimethylsilyl)pyrrolidine 4 was synthesized from the reaction of N-Boc-pyrrolidine 1 with trimethylsilyl chloride (TMSCl) at optional temperature in one-pot in good yield.
1 Experimental ORGANIC chemical derivatization of fullerene by cycloaddition reactions has attracted in-tense interest. It has been found that C<sub>60</sub> can undergo a series of cycloaddition reactions...1 Experimental ORGANIC chemical derivatization of fullerene by cycloaddition reactions has attracted in-tense interest. It has been found that C<sub>60</sub> can undergo a series of cycloaddition reactions associ-ated with poorly-conjugated and electron-deficient alkenes, including [4+2], [3+2], [2+2] and [2+1] cycloaddition reaction, 1, 3-dipolar cycloaddition reactions. [3+2] cycloaddi-tion reactions of azomethine ylides to C<sub>60</sub> have been widely used to prepare N-substituted展开更多
OBJECTIVE:To evaluate the therapeutic effectiveness of salidroside(Sal)and pyrrolidine dithiocarbamate(PDTC)against severe acute pancreatitis(SAP)in a rat model.METHODS:Rat models of SAP were established by retrograde...OBJECTIVE:To evaluate the therapeutic effectiveness of salidroside(Sal)and pyrrolidine dithiocarbamate(PDTC)against severe acute pancreatitis(SAP)in a rat model.METHODS:Rat models of SAP were established by retrograde infusion of sodium taurocholate solution.SAP rats were randomly divided into 6 groups:SAP 3 h group,SAP 24 h group,low-dose Sal treatment group(Sal L+S),middle-dose Sal treatment group(Sal M+S),high-dose Sal treatment group(Sal H+S)and PDTC treatment group(PDTC+S).The serum amylase,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)levels were determined by optical turbidimetry and enzyme-linked immunosorbent assay.The expression of Beclin-1,microtubule-associated protein light chain 3Ⅱ(LC3Ⅱ),lysosome associated membrane protein 2(LAMP2),interleukin-1 receptor associated kinase 1(IRAK1),inhibitorαof nuclear transcription factor-κB(IκBα),nuclear transcription factor-κB 65(p65)in the pancreas tissues were detected by quantitative real-time polymerase chain reaction and Western blot,while the pIκBαand p-p65 levels were detected by Western blot.Pathological changes of the pancreas and all the other indexes were observed at 3 and 24 h after operation.RESULTS:The serum IL-10 level,IκBαand LAMP2 levels in Sal M+S,Sal H+S and PDTC+S groups were higher than those in SAP 24 h group,while all the other indexes in these three groups were all lower significantly than those in SAP 24 h group.There was no significant difference in all indexes between Sal H+S and PDTC+S groups.CONCLUSION:High-dose Sal has an effectively therapeutic effect on SAP in rats,which was similar to PDTC.展开更多
Tri(o-bromobenzyl)tin diethyldithiocarbamate(1) and tri(m-fluorobenzyl)tin pyrrolidine dithiocarbamate(2) have been synthesized and characterized by elemental analysis, IR spectroscopy, NMR(~1 H, ^(13)C and ^(119)Sn),...Tri(o-bromobenzyl)tin diethyldithiocarbamate(1) and tri(m-fluorobenzyl)tin pyrrolidine dithiocarbamate(2) have been synthesized and characterized by elemental analysis, IR spectroscopy, NMR(~1 H, ^(13)C and ^(119)Sn), thermogravimetric analysis and single-crystal X-ray diffraction. The two complexes crystallize in the triclinic system space group P1. For complex 1, a = 0.9770(1), b = 1.1011(1), c = 1.4583(1) nm, α = 78.431(1)°, β = 86.307(1)°, γ = 69.712(1)°, V = 1.4417(2) nm^3, Z = 2, Dc = 1.790 g/cm^3, m(Mo Kα) = 52.04 cm–1, F(000) = 756, R = 0.0434 and wR = 0.0593. For complex 2, a = 0.7055(1), b = 1.3349(3), c = 1.3782(3) nm, α = 89.216(2)°, β = 82.044(2)°, γ = 84.637(2)°, V = 1.2799(5) nm^3, Z = 2, Dc = 1.537 g/cm^3, m(Mo Kα) = 11.98 cm^(–1), F(000) = 596, R = 0.0313 and wR = 0.0333. The two complexes represent mononuclear structures with five-coordinated [SnC3S2] cores forming a distorted trigonal bipyramid. The quantum chemical calculations of 1 and 2 have been investigated. The antitumor activity shows that 1 and 2 have higher activities than cisplatinum against Colo205, HepG2, MCF-7, Hela and H460 cell line in vitro.展开更多
Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic ab...Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic absorbed constituents in rat plasma after oral administration of CP extract.However,their structures were unclear due to the presence of various isomers and the lack of reference standards.In the present study,an MS-guided targeted isolation of pyrrolidine alkaloids of CP extract was performed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC/Q-TOF MS).For data analysis under fast data directed acquisition mode(Fast-DDA),an effective approach named characteristic fragmentation-assisted mass spectral networking was successfully applied to discover new pyrrolidine alkaloids with high MS response in CP extract.As a result,seven new pyrrolizidine alkaloids[codonopyrrolidiums C–I(3–9)],together with two known ones(1 and 2),were isolated and identified by NMR spectral analysis.Among them,codonopyrrolidium B(1),codonopyrrolidium D(4)and codonopyrrolidium E(5)were evaluated for lipid-lowering activity,and they could improve high fructose-induced lipid accumulation in HepG2 cells.In addition,the characteristic MS/MS fragmentation patterns of these pyrrolizidine alkaloids were investigated,and 17 pyrrolidine alkaloids were identified.This approach could accelerate novel natural products discovery and characterize a class of natural products with MS/MS fragmentation patterns from similar chemical scaffolds.The research also provides a chemical basis for revealing in vivo effective substances in CP.展开更多
A new class of chiral pyrrolidine ligands have been successfully synthesized and their chiral induction abilities have been examined in the homogeneous catalytic enantioselective cyclo-propanation of styrene. 15-30% e...A new class of chiral pyrrolidine ligands have been successfully synthesized and their chiral induction abilities have been examined in the homogeneous catalytic enantioselective cyclo-propanation of styrene. 15-30% enantiomeric excess ( ee) has been achieved.展开更多
Objective:To investigate the effects of NF-κB inhibitor pyrrolidine dithiocarbamate hydrochloride(PDTC) on vascular endothelial growth factor(VEGF) and endostatin expression in mice with Lewis lung cance;and its mech...Objective:To investigate the effects of NF-κB inhibitor pyrrolidine dithiocarbamate hydrochloride(PDTC) on vascular endothelial growth factor(VEGF) and endostatin expression in mice with Lewis lung cance;and its mechanism.Methods:Mice survival rate and anti-tumor effects were observed in different concentrations of NF-κB inhibitor PDTC after the Lewis lung cancer mice model was established.VEGF and endostatin expressions were detected by immunohistochemical assay.Results:Lewis lung cancer was be inhibited by 0.5 mg/kg.1.5 mg/kg and 3.0 mg/kg of NF-κB inhibitor PDTC(P<0.05).Microvessel density(MVD) in 0.5 mg/kg.1.5 mg/kg and 3.0 mg/kg NF-κB inhibitor PDTC groups were significantly lower than the control group(P<0.05).Immunohistochemical assay results showed that VEGF and endostatin expressions in the 0.5 mg/kg.1.5 mg/kg and 3.0 mg/kg NF-κB inhibitor PDTC groups were significantly lower than the control group(P<0.05).Western blot results also showed that NF-κB inhibitor PDTC could inhibit VEGF and endostatin expressions in tumor tissues.Conclusions:NF-κB inhibitor PDTC can inhibit tumor formation and reduce tumor angiogenesis in mice with Lewis lung cancer;and its mechanism maybe associated to VEGF and endostatin down-regulation.展开更多
AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine(SAM) decreases hepatitis C virus(HCV) expression.METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell cu...AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine(SAM) decreases hepatitis C virus(HCV) expression.METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell culture system. Huh7 HCV-replicon cells were treated with 1 mmol/L SAM for different times(24-72 h), then total RNA and proteins were isolated. c DNA was synthesized and real time-PCR was achieved to quantify HCV-RNA, superoxide dismutase 1 and 2(SOD-1, SOD-2) catalase, thioredoxin 1, methionine adenosyltransferase 1A and 2A(MAT1A, MAT2A) expression, and GAPDH and RPS18 as endogenous genes. Expression of cellular and viral protein was evaluated by western-blot analysis using antibodies vs HCV-NS5 A, SOD-1, SOD-2, catalase, thioredoxin-1, MAT1 A, MAT2 A, GAPDH and actin. Total glutathione levels were measured at different times by Ellman's recycling method(0-24 h). Reactive oxidative species(ROS) levels were quantified by the dichlorofluorescein assay(0-48 h); Pyrrolidin dithiocarbamate(PDTC) was tested as an antioxidant control and H2O2 as a positive oxidant agent.RESULTS: SAM exposition decreased HCV-RNA levels 50%-70% compared to non-treated controls(24-72 h). SAM induced a synergic antiviral effect with standard IFN treatment but it was independent of IFN signaling. In addition, 1 mmol/L SAM exposition did not modify viral RNA stability, but it needs cellular translation machinery in order to decrease HCV expression. Total glutathione levels increased upon SAM treatment in HCV-replicon cells. Transcriptional antioxidant enzyme expression(SOD-1, SOD-2 and thioredoxin-1) was increased at different times but interestingly, there was no significant change in ROS levels upon SAM treatment, contrary to what was detected with PDTC treatment, where an average 40% reduction was observed in exposed cells. There was a turnover from MAT1A/MAT2 A, since MAT1 A expression was increased(2.5 fold-times at 48 h) and MAT2 A was diminished(from 24 h) upon SAM treatment at both the transcriptional and translational level. CONCLUSION: A likely mechanism(s) by which SAM diminish HCV expression could involve modulating antioxidant enzymes, restoring biosynthesis of glutathione and switching MAT1/MAT2 turnover in HCV expressing cells.展开更多
R(+)-Citronellal was converted into a key intermediate,(unsaturated ketone 5)in three steps,which led to 6 having the frame ofarteannuic acid through intramolecular ene reaction.Further modification of 6afforded 1,6-e...R(+)-Citronellal was converted into a key intermediate,(unsaturated ketone 5)in three steps,which led to 6 having the frame ofarteannuic acid through intramolecular ene reaction.Further modification of 6afforded 1,6-epimer of dihydroarteannuic acid.The configuration of 7 wasdetermined by X-ray diffraction analysis.展开更多
Optically active copolymers of pairs of three monomers, triphenyl （methyl methacrylate）and one or two pyridyl substituted methyl methacrylate homologues, were obtained by helix-sense-selective copolymerization using...Optically active copolymers of pairs of three monomers, triphenyl （methyl methacrylate）and one or two pyridyl substituted methyl methacrylate homologues, were obtained by helix-sense-selective copolymerization using complexes of organolithium with chiral ligand as anionicinitiators in toluene at low temperature. The copolymers obtained with （-）-sparteine （Sp） and（S,S）-（+）-and （R, R）-（-）-2, 3-dimethoxy-1, 4-bis （dimethylamino） butanes（（+）-and （-）-DDB） complexes of organolithium showed low optical activity, but PMP complex with N, N-diphenylethyleneamine monolithium amide （PMP-DPEDA-Li） was effective in synthesizingcopolymers of high optical rotation ([α]<sub>D</sub><sup>25</sup> about+320～1370°)which were comparable to thoseof relative homopolymers with one-handed helical structure.展开更多
The novel well-defined chiral bicyclic thioureas based on enantiopure unsymmetric cis-2,5-disustituted pyrrolidine skeleton were firstly synthesized and fully characterized by their 1H NMR, 13C NMR and HRMS. Their abs...The novel well-defined chiral bicyclic thioureas based on enantiopure unsymmetric cis-2,5-disustituted pyrrolidine skeleton were firstly synthesized and fully characterized by their 1H NMR, 13C NMR and HRMS. Their absolute configurations were also determined by single-crystal X-ray analysis.展开更多
A novel class of aminopyrrolidinyl phosphonates was synthesized in 74% - 80% isolated yield by the addition of three-fold excess of primary amines to diethyl 4-chloro-1-butynylphosphonates. The reaction was carried ou...A novel class of aminopyrrolidinyl phosphonates was synthesized in 74% - 80% isolated yield by the addition of three-fold excess of primary amines to diethyl 4-chloro-1-butynylphosphonates. The reaction was carried out at room temperature and in the absence of solvent or catalyst to give solely compounds which showed predicted biological activity based on PASS program. Some of the synthesized derivatives of antibiotics exhibit properties for the treatment of stroke, the treatment of acute neurological disorders, and can also be acetyl esterase inhibitors.展开更多
This article describes the synthesis of some novel sulfonamides having the biologically active, thi-azole 4-6, 8, 10-12a,b, 20, 22, 34, 35, imidazo[1,2-a]pyridine 14, imidazo[2,1-c][1,2,4]triazole 15, imidazo[2,1-b]th...This article describes the synthesis of some novel sulfonamides having the biologically active, thi-azole 4-6, 8, 10-12a,b, 20, 22, 34, 35, imidazo[1,2-a]pyridine 14, imidazo[2,1-c][1,2,4]triazole 15, imidazo[2,1-b]thiazole 23, 24, 33, nicotinonitrile 25, 1,3,4-thiadiazine 27, quinoxaline 30 and 1,4-thiazine 31 moieties, starting with 1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1). The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR and Ms spectral data. All the compounds were tested in-vitro antihuman liver hepatocellular carcinoma cell line (HepG2). Compounds 8, 11, 4, 22, 12a, 33, 35, 27 and 24 with selectivity index (SI) values of 33.21, 30.49, 19.43, 14.82, 10.29, 7.3, 6.87, 6.15 and 4.62, respectively, exhibited better activity than methotrexate (MTX) as a reference drug with SI value of 4.14. Molecular Operating Environment (MOE) performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some synthesized compounds are suitable inhibitors against dihydrofolate reductase (DHFR) enzyme (PDB ID: 4DFR) with further modification.展开更多
Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides andβ-trifluoromethyl-substituted alkenyl heteroarenes was developed for the first time.A wide range of enantioenriched pyrrolidines containin...Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides andβ-trifluoromethyl-substituted alkenyl heteroarenes was developed for the first time.A wide range of enantioenriched pyrrolidines containing both heteroarenes and trifluoromethyl group with multiple stereogenic centers could be readily accessible by this method with good to high yields and excellent levels of both stereo-and regioselectivity(up to 99%yield,>20:1 rr,>20:1 dr,and up to 95%ee).Notably,substratecontrolled umpolung-type dipolar cycloaddition was also disclosed in this protocol to achieve regiodivergent synthesis withα-aryl substituted aldimine esters as the dipole precursors.Systematic DFT studies were conducted to explore the origin of the stereo-and regioselectivity of this 1,3-dipolar cycloaddition,and suggest that copper(Ⅱ)salt utilized in this catalytic system could be reduced in-situ to the active copper(Ⅰ)species and might be responsible for the observed high stereo-and regioselectivity.展开更多
A pyrrolidino[60]fullerene 1 with pyrrolidine group was synthesized and characterized. The UV-Vis spectra showed that the blue shift of absorption peaks was first observed when strong organic acids such as p-toluene s...A pyrrolidino[60]fullerene 1 with pyrrolidine group was synthesized and characterized. The UV-Vis spectra showed that the blue shift of absorption peaks was first observed when strong organic acids such as p-toluene sulfo-nic or trifluoroacetic acid were added to the solution of pyr-rolidino[60]fullerene 1 in dichloromethane. The results indicated that the pyrrolidino[60]fullerene derivatives without pyrrolidine group also possess the same phenomenon. Experiments and computation with the MOPAC 7.0 semi-empirical PM3 method demonstrated the reason that some energy gaps on [60]fullerene skeleton were increased because electronic charges on [60]fullerene framework transferred to pyrrolidine ring when strong organic acids were added into pyrrolidino[60]fullerene derivatives’ solution; as the result, the complexes could be formed and some absorption wavelengths blue shifted in the UV-Vis spectrum.展开更多
文摘BACKGROUND: The nuclear translocation of transcription factors may be a critical factor in the intracellular pathway involved in ischemia/reperfusion(I/R) injury. The aim of the study was to evaluate the role of nuclear factor-kappa B (NF-κB) in the pathogenesis of liver injury induced by intestinal ischemia/reperfusion (IIR) and to investigate the effect of pyrrolidine dithiocarbamate (PDTC) on this liver injury. METHODS: Male Wistar rats were divided randomly into three experimental groups (8 rats in each): sham operation group (control group); intestinal/reperfusion group(I/R group): animals received 1-hour of intestinal ischemia and 2-hour reperfusion; and PDTC treatment group (PDTC group): animals that received I/R subject to PDTC treatment (100 mg/kg). The histological changes in the liver and intestine were observed, and the serum levels of tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver superoxide dismutase (SOD), and nitrite/nitrate (NO) were measured. The immunohistochemical expression and Western blot analysis of liver NF-κB and intercellular adhesion molecule-1(ICAM-1) were observed. RESULTS: IIR induced liver injury characterized by the histological changes of liver edema, hemorrhage, polymorphonuclear neutrophil (PMN) infiltration, and elevated serum levels of AST and ALT. The serum TNF-α level was significantly higher than that of the control group(P【0.01) and a high level of liver oxidant product was observed (P【0.01). These changes were parallel to the positive expression of NF-κB and ICAM-1. After the administration of PDTC, the histological changes after liver injury were improved; the levels of SOD and NO in the liver were elevated and reduced, respectively (P【0.01). The expressions of ICAM-1 and NF-κB in the liver were weakened (P【0.01). CONCLUSION: NF-κB plays an important role in the pathogenesis of liver injury induced by HR. PDTC, an agent known to inhibit the activation of NF-κB, can reduce and prevent this injury.
基金supported by Surface Project of Shandong Provincial Natural Science Foundation(No.ZR2014HM081)
文摘Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.
文摘Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine(500 mg/kg), pyrrolidine dithiocarbamate(100 mg/kg), and saxagliptin(10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase(MAPK), phosphorylated extracellular signal-regulated kinase(ERK), c AMP response element-binding protein(CREB), interleukin-12(IL-12), caspase-3, β-defensin, inducible nitric oxide synthase(i NOS) and glucagon like peptide-1(GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, i NOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and i NOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.
文摘Studies have indicated that flavonoid luteolin is a potential inhibitor of tumor cell proliferation and may function as an anticarcinogenic agent. Pyrrolidine dithiocarbamate (PDTC), a synthetic compound, may exhibit biphasic effects on apoptosis depending on the experimental context. Previously, we found that luteolin induced the activation of the proapoptotic proteins, such as Bad, Bid, and Bax, in HL-60 human leukemia cells. We also explored the modulatory effects and molecular mechanisms of PDTC on the cytotoxicity of luteolin in HL-60 cells;PDTC could interfere with luteolin’s ability to cleave poly(ADP-ribose)-polymerase (PARP) and DNA fragmentation of factor-45 (DFF-45). In the current study, we further investigated the effect of PDTC on the luteolin-induced death-receptor pathway and the cleavage of the Bcl-2 family members. We found that the combination of luteolin and PDTC increased the survival of the HL-60 cells such that PDTC inhibited both extrinsic and intrinsic pathways in luteolin-induced apoptosis.
基金the National Natural Science Foundation of China (No 29772004).
文摘N-Boc-2, 5-bis(trimethylsilyl)pyrrolidine 4 was synthesized from the reaction of N-Boc-pyrrolidine 1 with trimethylsilyl chloride (TMSCl) at optional temperature in one-pot in good yield.
文摘1 Experimental ORGANIC chemical derivatization of fullerene by cycloaddition reactions has attracted in-tense interest. It has been found that C<sub>60</sub> can undergo a series of cycloaddition reactions associ-ated with poorly-conjugated and electron-deficient alkenes, including [4+2], [3+2], [2+2] and [2+1] cycloaddition reaction, 1, 3-dipolar cycloaddition reactions. [3+2] cycloaddi-tion reactions of azomethine ylides to C<sub>60</sub> have been widely used to prepare N-substituted
基金Supported by the Traditional Chinese Medicine Technology Development Plan Project of Jiangsu Province in 2020:Basic and Clinical Study on Salidroside in the Adjuvant Treatment of Severe Acute Pancreatitis(No.YB2020088)the Health Innovation Project of Lvyang Jinfeng Plan of Yangzhou City in 2020:Basic and Clinical Study on Salidroside in the Adjuvant Treatment of Severe Acute Pancreatitis(No.LJ202037)。
文摘OBJECTIVE:To evaluate the therapeutic effectiveness of salidroside(Sal)and pyrrolidine dithiocarbamate(PDTC)against severe acute pancreatitis(SAP)in a rat model.METHODS:Rat models of SAP were established by retrograde infusion of sodium taurocholate solution.SAP rats were randomly divided into 6 groups:SAP 3 h group,SAP 24 h group,low-dose Sal treatment group(Sal L+S),middle-dose Sal treatment group(Sal M+S),high-dose Sal treatment group(Sal H+S)and PDTC treatment group(PDTC+S).The serum amylase,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)levels were determined by optical turbidimetry and enzyme-linked immunosorbent assay.The expression of Beclin-1,microtubule-associated protein light chain 3Ⅱ(LC3Ⅱ),lysosome associated membrane protein 2(LAMP2),interleukin-1 receptor associated kinase 1(IRAK1),inhibitorαof nuclear transcription factor-κB(IκBα),nuclear transcription factor-κB 65(p65)in the pancreas tissues were detected by quantitative real-time polymerase chain reaction and Western blot,while the pIκBαand p-p65 levels were detected by Western blot.Pathological changes of the pancreas and all the other indexes were observed at 3 and 24 h after operation.RESULTS:The serum IL-10 level,IκBαand LAMP2 levels in Sal M+S,Sal H+S and PDTC+S groups were higher than those in SAP 24 h group,while all the other indexes in these three groups were all lower significantly than those in SAP 24 h group.There was no significant difference in all indexes between Sal H+S and PDTC+S groups.CONCLUSION:High-dose Sal has an effectively therapeutic effect on SAP in rats,which was similar to PDTC.
基金Supported by the Open Fund Project of Innovation Platform Hunan Province Higher Educational Institutions(18K089)the Fund for the Applied Key Discipline of Hunan Province+1 种基金the Support Plan for University Science and Technology Innovation Team of Hunan ProvinceAid programs for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province。
文摘Tri(o-bromobenzyl)tin diethyldithiocarbamate(1) and tri(m-fluorobenzyl)tin pyrrolidine dithiocarbamate(2) have been synthesized and characterized by elemental analysis, IR spectroscopy, NMR(~1 H, ^(13)C and ^(119)Sn), thermogravimetric analysis and single-crystal X-ray diffraction. The two complexes crystallize in the triclinic system space group P1. For complex 1, a = 0.9770(1), b = 1.1011(1), c = 1.4583(1) nm, α = 78.431(1)°, β = 86.307(1)°, γ = 69.712(1)°, V = 1.4417(2) nm^3, Z = 2, Dc = 1.790 g/cm^3, m(Mo Kα) = 52.04 cm–1, F(000) = 756, R = 0.0434 and wR = 0.0593. For complex 2, a = 0.7055(1), b = 1.3349(3), c = 1.3782(3) nm, α = 89.216(2)°, β = 82.044(2)°, γ = 84.637(2)°, V = 1.2799(5) nm^3, Z = 2, Dc = 1.537 g/cm^3, m(Mo Kα) = 11.98 cm^(–1), F(000) = 596, R = 0.0313 and wR = 0.0333. The two complexes represent mononuclear structures with five-coordinated [SnC3S2] cores forming a distorted trigonal bipyramid. The quantum chemical calculations of 1 and 2 have been investigated. The antitumor activity shows that 1 and 2 have higher activities than cisplatinum against Colo205, HepG2, MCF-7, Hela and H460 cell line in vitro.
基金The work was supported by the Science and Technology Projects in Guangzhou(No.202201010484)。
文摘Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic absorbed constituents in rat plasma after oral administration of CP extract.However,their structures were unclear due to the presence of various isomers and the lack of reference standards.In the present study,an MS-guided targeted isolation of pyrrolidine alkaloids of CP extract was performed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC/Q-TOF MS).For data analysis under fast data directed acquisition mode(Fast-DDA),an effective approach named characteristic fragmentation-assisted mass spectral networking was successfully applied to discover new pyrrolidine alkaloids with high MS response in CP extract.As a result,seven new pyrrolizidine alkaloids[codonopyrrolidiums C–I(3–9)],together with two known ones(1 and 2),were isolated and identified by NMR spectral analysis.Among them,codonopyrrolidium B(1),codonopyrrolidium D(4)and codonopyrrolidium E(5)were evaluated for lipid-lowering activity,and they could improve high fructose-induced lipid accumulation in HepG2 cells.In addition,the characteristic MS/MS fragmentation patterns of these pyrrolizidine alkaloids were investigated,and 17 pyrrolidine alkaloids were identified.This approach could accelerate novel natural products discovery and characterize a class of natural products with MS/MS fragmentation patterns from similar chemical scaffolds.The research also provides a chemical basis for revealing in vivo effective substances in CP.
基金Project supported by the National Natural Science Foundation of China (NO. 29790120) and Chinese Academy of Sciences (No.KJ951-A1-506-04).
文摘A new class of chiral pyrrolidine ligands have been successfully synthesized and their chiral induction abilities have been examined in the homogeneous catalytic enantioselective cyclo-propanation of styrene. 15-30% enantiomeric excess ( ee) has been achieved.
基金supported by Natural Science Fund Project of Liaoning Province.No.:201102050
文摘Objective:To investigate the effects of NF-κB inhibitor pyrrolidine dithiocarbamate hydrochloride(PDTC) on vascular endothelial growth factor(VEGF) and endostatin expression in mice with Lewis lung cance;and its mechanism.Methods:Mice survival rate and anti-tumor effects were observed in different concentrations of NF-κB inhibitor PDTC after the Lewis lung cancer mice model was established.VEGF and endostatin expressions were detected by immunohistochemical assay.Results:Lewis lung cancer was be inhibited by 0.5 mg/kg.1.5 mg/kg and 3.0 mg/kg of NF-κB inhibitor PDTC(P<0.05).Microvessel density(MVD) in 0.5 mg/kg.1.5 mg/kg and 3.0 mg/kg NF-κB inhibitor PDTC groups were significantly lower than the control group(P<0.05).Immunohistochemical assay results showed that VEGF and endostatin expressions in the 0.5 mg/kg.1.5 mg/kg and 3.0 mg/kg NF-κB inhibitor PDTC groups were significantly lower than the control group(P<0.05).Western blot results also showed that NF-κB inhibitor PDTC could inhibit VEGF and endostatin expressions in tumor tissues.Conclusions:NF-κB inhibitor PDTC can inhibit tumor formation and reduce tumor angiogenesis in mice with Lewis lung cancer;and its mechanism maybe associated to VEGF and endostatin down-regulation.
基金Supported by CONACYT-Mexico,grant register CB2010-01-155082 to Rivas-Estilla AM
文摘AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine(SAM) decreases hepatitis C virus(HCV) expression.METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell culture system. Huh7 HCV-replicon cells were treated with 1 mmol/L SAM for different times(24-72 h), then total RNA and proteins were isolated. c DNA was synthesized and real time-PCR was achieved to quantify HCV-RNA, superoxide dismutase 1 and 2(SOD-1, SOD-2) catalase, thioredoxin 1, methionine adenosyltransferase 1A and 2A(MAT1A, MAT2A) expression, and GAPDH and RPS18 as endogenous genes. Expression of cellular and viral protein was evaluated by western-blot analysis using antibodies vs HCV-NS5 A, SOD-1, SOD-2, catalase, thioredoxin-1, MAT1 A, MAT2 A, GAPDH and actin. Total glutathione levels were measured at different times by Ellman's recycling method(0-24 h). Reactive oxidative species(ROS) levels were quantified by the dichlorofluorescein assay(0-48 h); Pyrrolidin dithiocarbamate(PDTC) was tested as an antioxidant control and H2O2 as a positive oxidant agent.RESULTS: SAM exposition decreased HCV-RNA levels 50%-70% compared to non-treated controls(24-72 h). SAM induced a synergic antiviral effect with standard IFN treatment but it was independent of IFN signaling. In addition, 1 mmol/L SAM exposition did not modify viral RNA stability, but it needs cellular translation machinery in order to decrease HCV expression. Total glutathione levels increased upon SAM treatment in HCV-replicon cells. Transcriptional antioxidant enzyme expression(SOD-1, SOD-2 and thioredoxin-1) was increased at different times but interestingly, there was no significant change in ROS levels upon SAM treatment, contrary to what was detected with PDTC treatment, where an average 40% reduction was observed in exposed cells. There was a turnover from MAT1A/MAT2 A, since MAT1 A expression was increased(2.5 fold-times at 48 h) and MAT2 A was diminished(from 24 h) upon SAM treatment at both the transcriptional and translational level. CONCLUSION: A likely mechanism(s) by which SAM diminish HCV expression could involve modulating antioxidant enzymes, restoring biosynthesis of glutathione and switching MAT1/MAT2 turnover in HCV expressing cells.
文摘R(+)-Citronellal was converted into a key intermediate,(unsaturated ketone 5)in three steps,which led to 6 having the frame ofarteannuic acid through intramolecular ene reaction.Further modification of 6afforded 1,6-epimer of dihydroarteannuic acid.The configuration of 7 wasdetermined by X-ray diffraction analysis.
基金This project is supported by the National Natural Science Foundation of China and the President Foundation of Academia Sinica
文摘Optically active copolymers of pairs of three monomers, triphenyl （methyl methacrylate）and one or two pyridyl substituted methyl methacrylate homologues, were obtained by helix-sense-selective copolymerization using complexes of organolithium with chiral ligand as anionicinitiators in toluene at low temperature. The copolymers obtained with （-）-sparteine （Sp） and（S,S）-（+）-and （R, R）-（-）-2, 3-dimethoxy-1, 4-bis （dimethylamino） butanes（（+）-and （-）-DDB） complexes of organolithium showed low optical activity, but PMP complex with N, N-diphenylethyleneamine monolithium amide （PMP-DPEDA-Li） was effective in synthesizingcopolymers of high optical rotation ([α]<sub>D</sub><sup>25</sup> about+320～1370°)which were comparable to thoseof relative homopolymers with one-handed helical structure.
文摘The novel well-defined chiral bicyclic thioureas based on enantiopure unsymmetric cis-2,5-disustituted pyrrolidine skeleton were firstly synthesized and fully characterized by their 1H NMR, 13C NMR and HRMS. Their absolute configurations were also determined by single-crystal X-ray analysis.
文摘A novel class of aminopyrrolidinyl phosphonates was synthesized in 74% - 80% isolated yield by the addition of three-fold excess of primary amines to diethyl 4-chloro-1-butynylphosphonates. The reaction was carried out at room temperature and in the absence of solvent or catalyst to give solely compounds which showed predicted biological activity based on PASS program. Some of the synthesized derivatives of antibiotics exhibit properties for the treatment of stroke, the treatment of acute neurological disorders, and can also be acetyl esterase inhibitors.
文摘This article describes the synthesis of some novel sulfonamides having the biologically active, thi-azole 4-6, 8, 10-12a,b, 20, 22, 34, 35, imidazo[1,2-a]pyridine 14, imidazo[2,1-c][1,2,4]triazole 15, imidazo[2,1-b]thiazole 23, 24, 33, nicotinonitrile 25, 1,3,4-thiadiazine 27, quinoxaline 30 and 1,4-thiazine 31 moieties, starting with 1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1). The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR and Ms spectral data. All the compounds were tested in-vitro antihuman liver hepatocellular carcinoma cell line (HepG2). Compounds 8, 11, 4, 22, 12a, 33, 35, 27 and 24 with selectivity index (SI) values of 33.21, 30.49, 19.43, 14.82, 10.29, 7.3, 6.87, 6.15 and 4.62, respectively, exhibited better activity than methotrexate (MTX) as a reference drug with SI value of 4.14. Molecular Operating Environment (MOE) performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some synthesized compounds are suitable inhibitors against dihydrofolate reductase (DHFR) enzyme (PDB ID: 4DFR) with further modification.
基金supported by the National Natural Science Foundation of China(22071186,22071187,22073067,22101216,22271226,21933003,22193020,22193023)the National Youth Talent Support Program+3 种基金the Natural Science Foundation of Hubei Province(2020CFA0362021CFA069)the Fundamental Research Funds for the Central Universities(2042022kf1180,2042022kf1040)the Shenzhen Nobel Prize Scientists Laboratory Project(C17783101)the Guangdong Provincial Key Laboratory of Catalytic Chemistry(2020B121201002)。
文摘Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides andβ-trifluoromethyl-substituted alkenyl heteroarenes was developed for the first time.A wide range of enantioenriched pyrrolidines containing both heteroarenes and trifluoromethyl group with multiple stereogenic centers could be readily accessible by this method with good to high yields and excellent levels of both stereo-and regioselectivity(up to 99%yield,>20:1 rr,>20:1 dr,and up to 95%ee).Notably,substratecontrolled umpolung-type dipolar cycloaddition was also disclosed in this protocol to achieve regiodivergent synthesis withα-aryl substituted aldimine esters as the dipole precursors.Systematic DFT studies were conducted to explore the origin of the stereo-and regioselectivity of this 1,3-dipolar cycloaddition,and suggest that copper(Ⅱ)salt utilized in this catalytic system could be reduced in-situ to the active copper(Ⅰ)species and might be responsible for the observed high stereo-and regioselectivity.
基金The work was supported by the National Natural Science Foundation of China (Grant No. 29871032) and the State MajorBasic Research Development Program (Grant No. G19990b4504).
文摘A pyrrolidino[60]fullerene 1 with pyrrolidine group was synthesized and characterized. The UV-Vis spectra showed that the blue shift of absorption peaks was first observed when strong organic acids such as p-toluene sulfo-nic or trifluoroacetic acid were added to the solution of pyr-rolidino[60]fullerene 1 in dichloromethane. The results indicated that the pyrrolidino[60]fullerene derivatives without pyrrolidine group also possess the same phenomenon. Experiments and computation with the MOPAC 7.0 semi-empirical PM3 method demonstrated the reason that some energy gaps on [60]fullerene skeleton were increased because electronic charges on [60]fullerene framework transferred to pyrrolidine ring when strong organic acids were added into pyrrolidino[60]fullerene derivatives’ solution; as the result, the complexes could be formed and some absorption wavelengths blue shifted in the UV-Vis spectrum.
