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Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study 被引量:10
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作者 Hong Zhang Yang Liu +1 位作者 Li-Kun Wang Na Wei 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2017年第5期493-496,共4页
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
关键词 Drug-induced liver injury Anti-tuberculosis drug pyrrolidine dithiocarbamate JAK2 STAT3
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Protective effect of pyrrolidine dithiocarbamate on liver injury induced by intestinal ischemia-reperfusion in rats 被引量:10
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作者 Xiao-Feng Tian, Ji-Hong Yao, Ying-Hua Li, Hai-Feng Gao, Zhen-Zhen Wang, Chun-Ming Yang and Shu-Sen Zheng Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China Department of Pharmacology, Dalian Medical University, Dalian 116027, China and Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine. Hangzhou 310003, China 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2006年第1期90-95,共6页
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
关键词 liver injury intestinal ischemia/reperfusion nuclear factor kappa B pyrrolidine dithiocarbamate
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Activation of nuclear factor-kappa B and effects of pyrrolidine dithiocarbamate on TNBS-induced rat colitis 被引量:13
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作者 KenChen You-MingLong +2 位作者 HuiWang LeiLan Zhen-HeLin 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第10期1508-1514,共7页
AIM: To explore the changes of nuclear factor-kappa B (NF-κB) DNA-binding activity, the expression of intercellular adhesion molecule-1(ICAM-1) regulated by IMF-κB at various times and to evaluate the effects of pyr... AIM: To explore the changes of nuclear factor-kappa B (NF-κB) DNA-binding activity, the expression of intercellular adhesion molecule-1(ICAM-1) regulated by IMF-κB at various times and to evaluate the effects of pyrrolidine dithiocarbamate (PDTC) on trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. METHODS: TNBS of 0.6 mL was mixed with ethanol of 0.3 mL solution and instilled into the lumen of the rat colon. The rat models were divided into 6 groups, which were killed at 24 h, 3, 7,14, and 21 d after enema. Colonic inflammation and damage were assessed by macroscopical and histological criteria. Activity of NF-κB DNA-binding was analyzed by electrophoresis mobility shift assays (EMSA). Expression of ICAM-1 was detected by in situ hybridization (ISH) and immunohistochemistry (IH). Then various doses of PDTC were injected into rat abdomen 30 min before enema with TNBS/ethanol as pretreatment. The rats were killed 4 h after enema and the colonic inflammation, myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and DNA-binding activity of NF-κB were assessed. Finally, PDTC was injected intraperitoneally after colitis was induced. Changes of morphology were assayed. RESULTS: During the first week, hyperemia, hemorrhage, edema and ulceration of the colonic mucosa appeared with predominant infiltration of leukocytes. Neutrophils, macrophages, lymphocytes infiltrated in mucosa and submucosa 14 d later. Fibroblasts and granuloma-like structures were also obviously seen. The binding activity of NF-κB began to increase at 24 h time point and reached a peak at 14 d, then decreased but still was higher than control group at 21 d (P<0.01). Levels of ICAM-1 mRNA and protein significantly elevated at 24 h and the peak was at 21 d. Pretreatment with PDTC could attenuate the development of inflammation but not by reducing NF-KB activity. This attenuation of inflammation had a positive relationship with the dose of PDTC. PDTC at the dose of 100 mg/kg had no therapeutic effect after colitis was induced. CONCLUSION: NF-κB activation is an important event that may be involved in acute and chronic inflammation development and may contribute to self-protection against early inflammation damage. NF-κB also regulates ICAM-1 expression during colonic inflammation. Pretreatment of PDTC may attenuate the inflammation development. But PDTC has no therapeutic effect after the colitis is induced. 展开更多
关键词 Nuclear factor pyrrolidine dithiocarbamate RAT COLITIS
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Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis 被引量:21
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作者 Ichiro Hirata Shingo Yasumoto +6 位作者 Ken Toshina Takuya Inoue Takashi Nishikawa Naoko Murano Mitsuyuki Murano Fang-Yu Wang Ken-ichi Katsu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第11期1666-1671,共6页
AIM: To evaluate the effect of pyrrolidine dithio- carbamate (PDTC; an NF-κB inhibitor) administered at low (50 mg/kg) and high (100 mg/kg) doses in suppressing colitis in mice with dextran sodium sulfate (DSS)-induc... AIM: To evaluate the effect of pyrrolidine dithio- carbamate (PDTC; an NF-κB inhibitor) administered at low (50 mg/kg) and high (100 mg/kg) doses in suppressing colitis in mice with dextran sodium sulfate (DSS)-induced colitis. METHODS: Mice were divided into a DSS-untreated group (normal group), DSS-treated control group, DSS+PDTC-treated groupⅠ(low-dose group), and DSS+PDTC-treated groupⅡ (high-dose group). In each group, the disease activity index score (DAI score), intestinal length, histological score, and the levels of activated NF-κB and inflammatory cytokines (IL-1β and TNF-α) in tissue were measured. RESULTS: The DSS+PDTC-treated groupⅡ exhibited suppression of shortening of intestinal length and reduction of DAI score. Activated NF-κB level and IL-1β and TNF-α levels were significantly lower in DSS+PDTC- treated groupⅡ. CONCLUSION: These findings suggest that PDTC is useful for the treatment of ulcerative colitis. 展开更多
关键词 Ulcerative colitis DSS-induced colitis pyrrolidine dithiocarbamate NF-κB MICE
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Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine 被引量:8
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作者 Ismail H Mallick Wen-Xuan Yang +1 位作者 Marc C Winslet Alexander M Seifalian 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第46期7308-7313,共6页
AIM: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO production, attenuates intestinal IR injury. METHODS: Eighteen male rats were randomly allocated into three groups: (a) sham; (b)... AIM: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO production, attenuates intestinal IR injury. METHODS: Eighteen male rats were randomly allocated into three groups: (a) sham; (b) IR, consisting of 30 min of intestinal ischemia, followed by 2-h period of reperfusion; and (c) PDTC treatment before IR. Intestinal microvascular perfusion (IMP) was monitored continuously by laser Doppler flowmetry. At the end of the reperfusion, serum samples for lactate dehydrogenase (LDH) levels and biopsies of ileum were obtained. HO activity in the ileum was assessed at the end of the reperfusion period. RESULTS: At the end of the reperfusion in the IR group, IMP recovered partially to 42.5% of baseline (P〈0.05 vs sham), whereas PDTC improved IMP to 67.3% of baseline (P〈0.01 vs IR). There was a twofold increase in HO activity in PDTC group (2 062.66±106.11) as compared to IR (842.3±85.12) (P〈0.001). LDH was significantly reduced (P〈0.001) in PDTC group (585.6±102.4) as compared to IR group (1 973.8±306.5). Histological examination showed that the ileal mucosa was significantly less injured in PDTC group as compared with IR group. CONCLUSION: Our study demonstrates that PDTC improves the IMP and attenuates IR injury of the intestine possibly via HO production. Additional studies are warranted to evaluate the clinical efficacy of PDTC in the prevention of IR injury of the small intestine. 展开更多
关键词 INTESTINE Ischemia-reperfusion injury Heme oxygenase pyrrolidine
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Pyrrolidine dithiocarbamate and saxagliptin ameliorate ulcerative colitis in rats 被引量:1
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作者 Berween Mahmoud Elmahmoudy Mai A.Abd El Fattah +1 位作者 Mohamed F.Elyamany Laila A.Rashed 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2019年第9期373-380,共8页
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
关键词 ULCERATIVE colitis Inflammatory MEDIATORS Oxidative stress pyrrolidine DITHIOCARBAMATE SAXAGLIPTIN THIOACETAMIDE
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Pyrrolidine Dithiocarbamate (PDTC) Attenuates Luteolin-Induced Apoptosis in Human Leukemia HL-60 Cells 被引量:1
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作者 Ming-Fen Lee Cheng-Ta Li +1 位作者 Ming-Dian Chen An-Chin Cheng 《Journal of Cancer Therapy》 2012年第6期1125-1131,共7页
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
关键词 Apoptosis pyrrolidine DITHIOCARBAMATE HL-60 Cells LUTEOLIN Death-Receptor Pathway Bcl-2 Family
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N-Alkoxyl Templates for Diastereoselective Pyrrolidine Synthesis
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作者 SongQingWANG OmarA.IBRAHIMI +1 位作者 PanLI KangZHAO 《Chinese Chemical Letters》 SCIE CAS CSCD 2004年第1期1-4,共4页
Intramolecular cyclization of N-alkoxyl amines are studied for the stereoselective preparation of 2, 4-disubstituted pyrrolidine derivatives. Reduction of oximes under acidic conditions by NaBH3CN afforded the corres... Intramolecular cyclization of N-alkoxyl amines are studied for the stereoselective preparation of 2, 4-disubstituted pyrrolidine derivatives. Reduction of oximes under acidic conditions by NaBH3CN afforded the corresponding nucleophilic hydroxylamine derivatives, which subsequently cyclized via SN2' mechanism to give the desired N-alkoxyl pyrrolidines. 展开更多
关键词 SN' reaction pyrrolidineS OXIME hydroxylamine.
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Improved Electrochemical Synthesis of Nitro-substituted 1-Aryl-2-pyrrolidinecarbonitriles
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作者 Wei LIU Yuan MA +1 位作者 Ying Wu YIN Yu Fen ZHAO 《Chinese Chemical Letters》 SCIE CAS CSCD 2006年第6期736-738,共3页
In this paper, we described an improved electrochemical method for synthesis of some 1-aryl-2-pyrrolidinecarbonitrile derivatives bearing an electron-withdrawing group (NO2). The electrochemical synthesis of titile ... In this paper, we described an improved electrochemical method for synthesis of some 1-aryl-2-pyrrolidinecarbonitrile derivatives bearing an electron-withdrawing group (NO2). The electrochemical synthesis of titile compounds has been successfully performed in an undivided cell in reasonable yields. 展开更多
关键词 Anodic cyanation NITRILE pyrrolidine electrochemistry.
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First Total Synthesis of Hyacinthacine A_6 from the Protected Derivative of Polyhydroxylated Pyrrolidine
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作者 ZHANG Tao-xiang ZHOU Ling CAO Xiao-ping 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2008年第4期469-472,共4页
(1S、2R、3R、5R、7aR)-1,2-Dihydroxy-3-hydroxy methyl-5-methylpyrrolizidine(hyacinthacine A6, I) was synthesized by Wittig's methodology via the reaction of aldehyde 6, prepared from the partially protected deriva... (1S、2R、3R、5R、7aR)-1,2-Dihydroxy-3-hydroxy methyl-5-methylpyrrolizidine(hyacinthacine A6, I) was synthesized by Wittig's methodology via the reaction of aldehyde 6, prepared from the partially protected derivative of polyhydroxylated pyrrolidine, with appropriated ylides, followed by cyclization through the intemal reductive amination process of the resulting a,B-unsaturated ketone 7, and total deprotection. 展开更多
关键词 Hyacinthacine A6 pyrrolidineS Wittig reaction CYCLIZATION
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Synthesis of 2S-Hydroxymethyl-3R, 4R-dihydroxypyrrolidine
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作者 Zhen CHEN Ren Yun WANG +1 位作者 Li Lian ZHU Xiao Tian LIANG (Institute of Materia Medica. Peking Union Medical College) (The Chinese Academy of Medical Sciences, Bejing 100050) 《Chinese Chemical Letters》 SCIE CAS CSCD 1999年第8期651-652,共2页
The sythesis of 2S-hydroxymethyl-3R, 4R-dihydroxypyrrolidine from D-arabinose was described in this paper.
关键词 polydroxylated pyrrolidine 2S-hydroxymethyl-3R 4R-dihydroxypyrrolidine D-arabinose
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One-Pot Synthesis of N-Boc-2, 5-bis(trimethylsilyl)pyrrolidine
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作者 Dong, JC Li, RT Cheng, TM 《Chinese Chemical Letters》 SCIE CAS CSCD 2001年第12期1061-1064,共4页
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.
关键词 N-Boc-2 5-bis(trimethylsilyl)pyrrolidine TRIMETHYLSILYLATION ONE-POT
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Conversion of 3,4-Dihydroxypyrrolidine-2,5-Dione to Maleimide through Tosylation and Mechanism Study by DFT
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作者 Maocai Yan Zhen Zhang +3 位作者 Jinhui Zhou Wei Li Shuai Fan Zhaoyong Yang 《Computational Chemistry》 2018年第3期47-56,共10页
Pyrrolidine-2,5-dione and maleimide are important scaffolds of many organic substances, and their derivatives are now attracting more and more interests from researchers in organic synthesis, medicinal chemistry, and ... Pyrrolidine-2,5-dione and maleimide are important scaffolds of many organic substances, and their derivatives are now attracting more and more interests from researchers in organic synthesis, medicinal chemistry, and drug development. Tosyloxy (-OTs) group is an important functional group widely used in organic synthesis, because it can be readily prepared from alcohols and is an excellent leaving group. However, surprisingly, substances bearing tosyloxy groups on pyrrolidine-2,5-dione or maleimide scaffolds are very rare. In this study, we discovered that, when treated with TsCl/Et3N,?trans-3,4-dihydroxypyrrolidine-2,5- dione will eliminate a TsOH molecule to form monotosyloxymaleimide. Thermodynamic and kinetic factors affecting this reaction were investigated by theoretical computation using density functional theory (DFT), and the possible reaction mechanism was proposed based on the computation results. Our results showed that tosylates of trans -3,4-dihydroxypyrrolidine- 2,5-dione, either monotosylate or ditosylate, are thermodynamically instable and may spontaneously convert to maleimides. This knowledge could be useful in understanding the properties of pyrrolidine-2,5-diones and maleimides, as well as the related organic synthesis. 展开更多
关键词 pyrrolidine-2 5-Dione MALEIMIDE Elimination Reaction MECHANISM Density Functional Theory
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Synthesis of Quinolone Analogues: 7-[(2S,4R)-2-Aminomethyl-4- hydroxypyrrolidin-1-yl] Quinolones
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作者 JiuYuLIU HuiYuanGUO 《Chinese Chemical Letters》 SCIE CAS CSCD 2004年第5期535-538,共4页
New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone- 3-carboxylic acids with (2S, 4R)-2-aminom... New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone- 3-carboxylic acids with (2S, 4R)-2-aminomethyl-4-hydroxypyrrolidine. These compounds were characterized by FAB-MS and 1H NMR. 展开更多
关键词 pyrrolidine QUINOLONE synthesis.
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An Aminopyrrolidinyl Phosphonates—A New Class of Antibiotics: Facile Synthesis and Predicted Biological Activity
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作者 Abed Al Aziz Al Quntar Hasan Dweik +2 位作者 Ahmad Jabareen Tatyana A. Gloriozova Valery M. Dembitsky 《International Journal of Organic Chemistry》 2020年第4期170-181,共12页
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
关键词 Alkynylphosphonates CYCLIZATION pyrrolidine β-Aminophosphonates Amine Addition ANTIBIOTICS
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Synthesis and Crystal Structure of Ethyl 3-(4-Chlorophenyl)-3,4-dihydro-6-methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate 被引量:2
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作者 胡扬根 徐靖 丁明武 《Chinese Journal of Structural Chemistry》 SCIE CAS CSCD 2009年第6期689-692,共4页
The crystal structure of the title compound ethyl 3-(4-chlorophenyl)-3,4-dihydro-6- methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate (C20H20ClN3O4, Mr= 401.84) has been prepared and determined... The crystal structure of the title compound ethyl 3-(4-chlorophenyl)-3,4-dihydro-6- methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate (C20H20ClN3O4, Mr= 401.84) has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215(9), b = 8.5311(4), c = 21.6886(9) A^°, β = 91.607(1)°, V = 3814.0(3)A^°^3, Z = 8, Dc = 1.400 g/cm^3, F(000) = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ(I). X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit. 展开更多
关键词 crystal structure ethyl 3-(4-ehlorophenyl)-3 4-dihydro-6-methyl-4-oxo-2- pyrrolidin-1-yl)furo[2 3-d]pyrimidine-5-earboxylate aza-Wittig reaction synthesis
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吡咯烷二硫代氨基甲酸铵对创伤性脑损伤大鼠神经炎症的作用及机制
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作者 杨家发 陆兆丰 +3 位作者 王亚琼 陆若玉 李海荣 刘梦佳 《新乡医学院学报》 CAS 2024年第7期631-639,共9页
目的探讨吡咯烷二硫代基甲酸铵(PDTC)对创伤性脑损伤(TBI)大鼠半暗带神经炎症损伤的作用及机制。方法将60只Sprague Dawley大鼠按随机数字表法分为PDTC组、TBI组、假手术组、对照组,每组15只。PDTC组大鼠于术前15 min腹腔注射PDTC(100 m... 目的探讨吡咯烷二硫代基甲酸铵(PDTC)对创伤性脑损伤(TBI)大鼠半暗带神经炎症损伤的作用及机制。方法将60只Sprague Dawley大鼠按随机数字表法分为PDTC组、TBI组、假手术组、对照组,每组15只。PDTC组大鼠于术前15 min腹腔注射PDTC(100 mg·kg-1),TBI组、假手术组及对照组大鼠腹腔注射等体积双蒸水。TBI组和PDTC组大鼠开颅窗后,将内径6.0 mm的2.5 g钢棒从内径7.0 mm聚氯乙烯透明管高度自75 cm自由下落,撞击硬脑膜致右顶叶脑挫裂伤,制备TBI模型;假手术组大鼠开颅窗后用骨蜡封闭,不施加打击;对照组大鼠正常饲养。造模后1、4、7 d,应用改良的神经损伤评分(mNSS)评估各组大鼠神经行为学损害程度;造模后2 d,取4组大鼠各5只,断头处死,取脑组织,行苏木精-伊红(HE)染色,光学显微镜下观察脑组织形态学改变;应用免疫组织化学染色检测各组大鼠脑组织中β-淀粉样前体蛋白(β-APP)及胶质纤维酸性蛋白(GFAP)表达。造模后24 h,4组大鼠各取5只,断头取右侧损伤半暗带组织,应用Western blot检测各组大鼠右侧损伤半暗带组织中核转录因子-κB(NF-κB)P65、磷酸化NF-κB P65、NF-κB抑制蛋白(IκB)、磷酸化IκB、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)及caspase-1蛋白的表达,实时定量聚合酶链式反应检测各组大鼠右侧损伤半暗带组织中NF-κB P65、IκB、NLRP3及caspase-1 mRNA的表达。结果造模后1、4、7 d,TBI组大鼠mNSS评分均显著高于PDTC、对照组、假手术组,PDTC组大鼠mNSS评分显著高于对照组和假手术组(P<0.05);假手术组与对照组大鼠mNSS评分比较差异无统计学意义(P>0.05)。对照组及假手术组大鼠的神经元及神经胶质细胞形态正常,无肿胀,细胞间质无增宽。TBI组大鼠脑组织出现弥漫性出血性改变,神经元胞体形态不一,细胞膜与细胞质分辨不清,细胞核固缩,常为三角形,正常结构及核仁皆消失,弥漫性白细胞、红细胞填充视野。PDTC组大鼠病灶周边呈缺血性改变,神经元体积轻度缩小,呈均匀淡红色,细胞核固缩,细胞核、质分离,正常结构及核仁皆消失,神经炎症局限化。对照组及假手术组大鼠脑组织无明显β-APP和GFAP表达,TBI组和PDTC组大鼠脑组织中均可见β-APP、GFAP在神经元浆膜下和(或)轴突处积累。与TBI组比较,PDTC组大鼠大脑皮质β-APP和GFAP阳性染色体神经元细胞数减少、表达强度减弱。假手术组、TBI组和PDTC组大鼠脑组织中NF-κB P65蛋白相对表达量显著高于对照组,PDTC组大鼠脑组织中NF-κB P65蛋白相对表达量显著高于TBI组(P<0.05)。PDTC组和假手术组大鼠脑组织中磷酸化NF-κB P65蛋白相对表达量显著低于对照组,TBI组大鼠脑组织中磷酸化NF-κB P65蛋白相对表达量显著高于对照组和假手术组,PDTC组大鼠脑组织中磷酸化NF-κB P65蛋白相对表达量显著低于TBI组和假手术组(P<0.05)。假手术组与对照组大鼠脑组织中IκB蛋白相对表达量比较差异无统计学意义(P>0.05);TBI组大鼠脑组织中IκB蛋白相对表达量显著高于对照组,PDTC组大鼠脑组织中IκB蛋白相对表达量显著低对照组、假手术组和TBI组(P<0.05)。TBI组大鼠脑组织中磷酸化IκB蛋白相对表达量显著低于对照组和假手术组,PDTC组大鼠脑组织中磷酸化IκB蛋白相对表达量高于TBI组(P<0.05)。假手术组大鼠脑组织中NLRP3蛋白相对表达量显著高于对照组,TBI组和PDTC组大鼠脑组织中NLRP3蛋白相对表达量显著低于假手术组和对照组,TBI组大鼠脑组织中NLRP3蛋白相对表达量显著低于PDTC组(P<0.05)。假手术组、PDTC组及TBI组大鼠脑组织中caspase-1蛋白相对表达量显著高于对照组,PDTC组大鼠脑组织中caspase-1蛋白相对表达量显著低于TBI组(P<0.05)。PDTC组、TBI组、假手术组大鼠脑组织中NF-κB P65 mRNA相对表达量显著高于对照组,PDTC组和TBI组大鼠脑组织中NF-κB P65 mRNA水平显著高于假手术组,PDTC组大鼠脑组织中NF-κB P65 mRNA相对表达量显著低于TBI组(P<0.05)。PDTC组和TBI组大鼠脑组织中IκB mRNA相对表达量显著低高对照组,假手术组大鼠脑组织中IκB mRNA表达显著低于对照组(P<0.05);PDTC组和TBI组大鼠脑组织中IκB mRNA相对表达量显著高于假手术组,PDTC组大鼠脑组织中IκB mRNA相对表达量显著低于TBI组(P<0.05)。PDTC组和TBI组大鼠脑组织中NLRP3 mRNA相对表达量显著高于对照组,假手术组大鼠脑组织中NLRP3 mRNA相对表达量显著低于对照组,PDTC组和TBI组大鼠脑组织中NLRP3 mRNA相对表达量显著高于假手术组,PDTC组大鼠脑组织中NLRP3 mRNA相对表达量显著低于TBI组(P<0.05)。假手术组、TBI组、PDTC组大鼠脑组织中caspase-1 mRNA相对表达量显著低于对照组,TBI组、PDTC组大鼠脑组织中caspase-1 mRNA相对表达量显著高于假手术组(P<0.05)。结论PDTC可有效改善TBI大鼠神经功能缺损评分、减轻神经炎症损伤,其机制可能通过调节NF-κB/NLRP3轴相关炎症损伤指标mRNA和蛋白表达及调控下游炎症因子而发挥作用。 展开更多
关键词 创伤性脑损伤 吡咯烷二硫代基甲酸铵 神经炎症损伤 核转录因子
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新型双螺环[吡咯啉酮-氧化吲哚-六氢山酮素]拼接化合物的合成及其抗人白血病细胞活性
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作者 王希瑞 徐客兰 +3 位作者 石庆辉 张敏 刘雄利 邓国栋 《合成化学》 CAS 2024年第10期866-873,共8页
天然产物优势骨架多样性衍生物库的构建是植物化学领域的一个重要课题。本文基于新的方法学策略,以不同取代基的底物色原酮-氧化吲哚合成子(1)和3-烯-2-羰基吡咯烷(2)发生[4+2]环加成反应,合成了10个未见文献报道的双螺环[吡咯啉酮-氧... 天然产物优势骨架多样性衍生物库的构建是植物化学领域的一个重要课题。本文基于新的方法学策略,以不同取代基的底物色原酮-氧化吲哚合成子(1)和3-烯-2-羰基吡咯烷(2)发生[4+2]环加成反应,合成了10个未见文献报道的双螺环[吡咯啉酮-氧化吲哚-六氢山酮素]拼接化合物(3a~3j),产率73%~85%,dr>20∶1。化合物3的结构经^(1)H NMR,^(13)C NMR和HR-MS(ESI-TOF)表征,化合物3j的相对构型通过单晶X-射线衍射进行了确定。采用MTT法研究了化合物3对人白血病细胞(K562)的体外抗肿瘤活性。结果表明:双螺环[吡咯啉酮-氧化吲哚-六氢山酮素]拼接化合物3b,3e,3g和3i对K562具有一定的抑制活性。 展开更多
关键词 六氢山酮素 3-烯-2-羰基吡咯烷 色原酮-氧化吲哚合成子 [4+2]环加成反应 抗人白血病活性
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光/电催化3-氮杂-1,5-二烯合成4-吡咯啉-2-酮的研究进展 被引量:1
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作者 龚开兴 马迎春 +1 位作者 余平 梁德强 《云南化工》 CAS 2024年第5期7-10,共4页
4-吡咯啉-2-酮是大量天然产物和药物分子的母核结构,其衍生物通常具有重要的生物活性。4-吡咯啉-2-酮的传统合成方法需要高温等苛刻条件,且需要使用贵金属做催化剂。最近发现,从易得的3-氮杂-1,5-二烯出发,可以一步合成官能团化4-吡咯啉... 4-吡咯啉-2-酮是大量天然产物和药物分子的母核结构,其衍生物通常具有重要的生物活性。4-吡咯啉-2-酮的传统合成方法需要高温等苛刻条件,且需要使用贵金属做催化剂。最近发现,从易得的3-氮杂-1,5-二烯出发,可以一步合成官能团化4-吡咯啉-2-酮衍生物,其中的光催化和电催化方法尤其绿色和温和,符合绿色化学理念和“双碳”目标的要求。根据反应类别进行分类,总结了光/电催化3-氮杂-1,5-二烯合成4-吡咯啉-2-酮的研究进展。 展开更多
关键词 4-吡咯啉-2-酮 光催化 合成电化学 烯烃
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新型保润剂丙二醇吡咯酯的制备及其对再造烟叶保润效果研究
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作者 楚文娟 樊文鹏 +5 位作者 高子婷 韩路 田海英 姬小明 万纪强 来苗 《轻工学报》 CAS 北大核心 2024年第2期87-93,共7页
为克服传统保润剂丙二醇在加热烟草制品中吸湿性过强的缺点,制备了一种新型保润剂丙二醇吡咯酯,并利用热重-微商热重-差示扫描量热法、热裂解气相色谱/质谱和低场核磁共振技术考查其热行为及其在再造烟叶中的保润效果。结果表明:丙二醇... 为克服传统保润剂丙二醇在加热烟草制品中吸湿性过强的缺点,制备了一种新型保润剂丙二醇吡咯酯,并利用热重-微商热重-差示扫描量热法、热裂解气相色谱/质谱和低场核磁共振技术考查其热行为及其在再造烟叶中的保润效果。结果表明:丙二醇吡咯酯的热失重区间为149.9~400.0℃,在298.7℃时质量损失率达最大(77.39%);在200℃、300℃和350℃下的主要裂解产物为吡咯酸和丙二醇,其中丙二醇可以起到协调和降低烟气干燥感的作用;在低湿环境下添加丙二醇吡咯酯的再造烟叶丝保润能力高于空白组,但低于丙二醇组;丙二醇组、丙二醇吡咯酯组和空白组中再造烟叶丝内部结合水占比分别为75%、70%、68%,即丙二醇吡咯酯可以降低再造烟叶丝的强吸湿性,同时保持一定的保润能力。 展开更多
关键词 丙二醇吡咯酯 保润剂 热行为 再造烟叶 加热卷烟
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