当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Repurposing ibuprofen to control Staphylococcus aureus biofilms.

Repurposing ibuprofen to control Staphylococcus aureus biofilms.

Abstract：

:Drug repurposing arises as an interesting alternative to overcome the limited efficacy of current available antibiotics by reducing time, cost and risk associated with drug innovation. In this study, the activity of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), was evaluated on the control of pre-established adhered cells (2 h) and 24 h old biofilms of Staphylococcus aureus. Bacterial adhesion was performed by S. aureus CECT 976, while biofilm formation was also performed by the antibiotic-resistant strains: SA1199B, RN4220 and XU212. The treatment with ibuprofen promoted metabolic reductions up to 80% and total loss of culturability of adhered cells and 24 h old biofilms. Ibuprofen demonstrated moderate efficacy to remove biofilms of S. aureus CECT 976 (removal ≤ 40%), but did not display removal action against the antibiotic-resistant strains. Antibacterial activity (inhibitory and bactericidal) and mode of action of ibuprofen were also assessed using different bacterial physiological indices. Minimum inhibitory and bactericidal concentrations of the four S. aureus strains ranged between 500 and 2000 mg L-1 and 1400 - >2000 mg L-1, respectively. After S. aureus CECT 976 incubation with ibuprofen, cell permeation to propidium iodide, release of intracellular potassium and changes on cell surface hydrophobicity were observed. The overall results, demonstrate that ibuprofen can control S. aureus planktonic and sessile growth, with strong destabilizing and disrupting action on the cytoplasmic membrane.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Oliveira IM,Borges A,Borges F,Simões M

doi

10.1016/j.ejmech.2019.01.046

subject

Has Abstract

pub_date

2019-03-15 00:00:00

pages

197-205

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(19)30061-3

journal_volume

166

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • 2-hydroxyisoquinoline-1,3(2H,4H)-diones as inhibitors of HIV-1 integrase and reverse transcriptase RNase H domain: influence of the alkylation of position 4.

    abstract：:We report herein the synthesis of a series of fifteen 2-hydroxyisoquinoline-1,3(2H,4H)-dione derivatives. Alkyl and arylalkyl groups were introduced on position 4 of the basis scaffold. All the compounds presented poor inhibitory properties against HIV-1 reverse transcriptase ribonuclease H (RNase H). Four compounds i...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.11.033

    authors： Billamboz M,Bailly F,Lion C,Calmels C,Andréola ML,Witvrouw M,Christ F,Debyser Z,De Luca L,Chimirri A,Cotelle P

    更新日期：2011-02-01 00:00:00

  • Design, synthesis and antitubercular evaluation of benzothiazinones containing a piperidine moiety.

    abstract：:We herein report the design and synthesis of benzothiazinones containing a piperidine moiety as new antitubercular agents based on the structure feature of IMB-ZR-1 discovered in our lab. Some of them were found to have good in vitro activity (MIC < 1 μg/mL) against drug-susceptible Mycobacterium tuberculosis H37RV st...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.03.060

    authors： Lv K,Tao Z,Liu Q,Yang L,Wang B,Wu S,Wang A,Huang M,Liu M,Lu Y

    更新日期：2018-05-10 00:00:00

  • Structure activity relationship studies of natural product chemokine receptor CCR5 antagonist anibamine toward the development of novel anti prostate cancer agents.

    abstract：:Recent studies have indicated that the CCR5 chemokine receptor may be a potential target for treating prostate cancer. Thus, development of CCR5 antagonists may provide novel prostate cancer therapy. Anibamine, a novel pyridine quaternary alkaloid isolated from Aniba sp., was found to effectively compete with (125)I-g...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.07.049

    authors： Zhang F,Arnatt CK,Haney KM,Fang HC,Bajacan JE,Richardson AC,Ware JL,Zhang Y

    更新日期：2012-09-01 00:00:00

  • Inhibitors of the kynurenine pathway.

    abstract：:Strokes (intracranial thomboses or haemorrhaging) cause death and disability, but effective treatments are lacking. The metabolism of tryptophan leads to the generation of quinolinic acid, an agonist potentially neurotoxic at glutamate receptors, and kynurenic acid, an antagonist at the same population of receptors. T...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/s0223-5234(00)00121-5

    authors： Stone TW

    更新日期：2000-02-01 00:00:00

  • Design, synthesis and antitumor activity of novel thiophene-pyrimidine derivatives as EGFR inhibitors overcoming T790M and L858R/T790M mutations.

    abstract：:Five series of novel thiophene-pyrimidine derivatives (9a-h, 10a-f, 11a-f, 12a-f, 13a-f) have been synthesized and tested for their anti-proliferative activity against several cancer cell lines in which EGF is highly expressed. Most of the target compounds showed excellent activity against one or more cancer cell line...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112511

    authors： Xiao Z,Zhou Z,Chu C,Zhang Q,Zhou L,Yang Z,Li X,Yu L,Zheng P,Xu S,Zhu W

    更新日期：2020-10-01 00:00:00

  • An overview on crystal structures of InhA protein: Apo-form, in complex with its natural ligands and inhibitors.

    abstract：:The enoyl-ACP reductase InhA from the mycobacterial fatty acid biosynthesis pathway has become a target of interest for the development of new anti-tubercular drugs. This protein has been identified as essential for the survival of Mycobacterium tuberculosis, the causative agent of tuberculosis, and as the main target...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2018.01.047

    authors： Chollet A,Maveyraud L,Lherbet C,Bernardes-Génisson V

    更新日期：2018-02-25 00:00:00

  • Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide.

    abstract：:Two novel series of 4-thiazolidinone derivatives, namely 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid [2-(5-nitro-2-furyl/substituted phenyl)-4-thiazolidinone-3-yl]amides (5a-g) and 2-(2',4'-difluoro-4-hydroxybiphenyl-3-carbonylhydrazono)-3-alkyl/aryl-4-thiazolidinones (6a-e) together with 5-(2',4'-difluoro-4-hy...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.11.005

    authors： Küçükgüzel G,Kocatepe A,De Clercq E,Sahin F,Güllüce M

    更新日期：2006-03-01 00:00:00

  • Synthesis, molecular docking and biological evaluation of Schiff base transition metal complexes as potential urease inhibitors.

    abstract：:Six transition metal compounds of Schiff base ligands were evaluated for the inhibitory activity on jack bean urease, of which compounds 2-6 were determined by single crystal X-ray analysis. It was found that copper(II) complexes 1 and 4 showed strong inhibitory activity against jack bean urease (IC(50) = 0.52 and 0.4...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.07.007

    authors： Chen W,Li Y,Cui Y,Zhang X,Zhu HL,Zeng Q

    更新日期：2010-10-01 00:00:00

  • Desing and synthesis of potent anti-Trypanosoma cruzi agents new thiazoles derivatives which induce apoptotic parasite death.

    abstract：:Chagas disease, caused by the kinetoplastid protozoan parasite Trypanosoma cruzi, remains a relevant cause of illness and premature death and it is estimated that 6 million to 7 million people are infected worldwide. Although chemotherapy options are limited presenting serious problems, such as low efficacy and high t...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.02.026

    authors： da Silva EB,Oliveira E Silva DA,Oliveira AR,da Silva Mendes CH,Dos Santos TA,da Silva AC,de Castro MC,Ferreira RS,Moreira DR,Cardoso MV,de Simone CA,Pereira VR,Leite AC

    更新日期：2017-04-21 00:00:00

  • Cyclopentadienyl ruthenium(II) carbosilane metallodendrimers as a promising treatment against advanced prostate cancer.

    abstract：:In searching for efficient and selective antitumour drugs, a new family of carbosilane metallodendrimers functionalized with [Ru(η5-C5H5)(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1] decane) is reported. Experiments of the biophysical characterization showed an ability to interact with biological membranes,...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112414

    authors： Sanz Del Olmo N,Bajo AM,Ionov M,García-Gallego S,Bryszewska M,Gómez R,Ortega P,de la Mata FJ

    更新日期：2020-08-01 00:00:00

  • Synthesis of dicationic diaryltriazines nucleic acid binding agents.

    abstract：:- The synthesis of 2,4-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-1,3,5-triazine 6a and 2,4-bis[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl]-1,3,5-triazine 6b in 3 steps from either 4-bromobenzamidine or 4-(carbamoyl)benzamidine is reported. The synthesis of 4,6-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-2-dimethylam...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/0223-5234(94)90061-2

    authors： Spychala J,Boykin D,Wilson W,Zhao M,Tidwell R,Dykstra C,Hall J,Jones S,Schinazi R

    更新日期：1994-01-01 00:00:00

  • Kinetic and in silico studies of novel hydroxy-based thymol analogues as inhibitors of mushroom tyrosinase.

    abstract：:The present studies reports the synthesis of hydoxylated thymol analogues (4a-e) and (6a-c) as mushroom tyrosinase inhibitors. The title compounds were obtained in good yield and characterized by FTIR, (1)H NMR, (13)C NMR, Mass spectral data and X-ray crystallography in case of compound (6a). The inhibitory effects on...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.05.031

    authors： Ashraf Z,Rafiq M,Seo SY,Kwon KS,Babar MM,Zaidi NU

    更新日期：2015-06-15 00:00:00

  • Structure-based drug design: Synthesis and biological evaluation of quinazolin-4-amine derivatives as selective Aurora A kinase inhibitors.

    abstract：:Aurora kinases play critical roles in the regulation of the cell cycle and mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family, is frequently highly expressed in tumors, and selective Aurora A inhibition serves as a significant component of anticancer therapy. However, designing highly sel...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.08.053

    authors： Long L,Wang YH,Zhuo JX,Tu ZC,Wu R,Yan M,Liu Q,Lu G

    更新日期：2018-09-05 00:00:00

  • 3-benzylamino-β-carboline derivatives induce apoptosis through G2/M arrest in human carcinoma cells HeLa S-3.

    abstract：:β-carboline derivatives are known as the lead compounds for anti-tumor agents. To examine an optimal structure for anti-tumor activity, we synthesized a variety of β-carboline derivatives, possessing a variety of substituents on the nitrogen atom of the amino group of 3-amino-β-carboline, and evaluated their anti-tumo...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.11.044

    authors： Ikeda R,Iwaki T,Iida T,Okabayashi T,Nishi E,Kurosawa M,Sakai N,Konakahara T

    更新日期：2011-02-01 00:00:00

  • Covalent allosteric modulation: An emerging strategy for GPCRs drug discovery.

    abstract：:Designing covalent allosteric modulators brings new opportunities to the field of drug discovery towards G-protein-coupled receptors (GPCRs). Targeting an allosteric binding pocket can allow a modulator to have protein subtype selectivity and low drug resistance. Utilizing covalent warheads further enables the modulat...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2020.112690

    authors： Bian Y,Jun JJ,Cuyler J,Xie XQ

    更新日期：2020-11-15 00:00:00

  • Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach.

    abstract：:A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis. Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pha...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.03.013

    authors： More UA,Joshi SD,Aminabhavi TM,Kulkarni VH,Badiger AM,Lherbet C

    更新日期：2015-04-13 00:00:00

  • Synthesis and pharmacological properties of a new hydrophilic and orally bioavailable 5-HT4 antagonist.

    abstract：:5-HT4 receptor antagonists have been suggested to have clinical potential in treatment of atrial fibrillation, diarrhea-prone irritable bowel syndrome and urinary incontinence. Recently, the use of 5-HT4 antagonists has been suggested to have a therapeutic benefit in heart failure. Affinity for the hERG potassium ion ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.03.060

    authors： Brudeli B,Moltzau LR,Nguyen CH,Andressen KW,Nilsen NO,Levy FO,Klaveness J

    更新日期：2013-06-01 00:00:00

  • LUMO energy of model compounds of bispyridinium compounds as an index for the inhibition of choline kinase.

    abstract：:Eleven derivatives of 1,1'-[1,2-ethylenebis(benzene-1,4-diylmethylene)]bis(4-pyridinium) dibromides bearing various groups at C-4 of the pyridinium moiety were synthesized and examined for their inhibition of choline kinase (ChoK) and antiproliferative activities. The C-4 substituents include electron-releasing, neutr...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(01)01219-3

    authors： Campos J,del Carmen Núñez M,Rodríguez V,Entrena A,Hernández-Alcoceba R,Fernández F,Lacal JC,Gallo MA,Espinosa A

    更新日期：2001-03-01 00:00:00

  • Copper(II/I) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline: synthesis, crystal structure, antitumor activity and DNA interaction.

    abstract：:Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu₂(PYP)₂Cl₄] (1), [Cu₄(PYP)₄(ClO₄)₂(H₂O)₂](ClO₄)₂·2H₂O (2), and [Cu₂(PYP)2Cl4]n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tum...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.10.031

    authors： Huang KB,Chen ZF,Liu YC,Wang M,Wei JH,Xie XL,Zhang JL,Hu K,Liang H

    更新日期：2013-01-01 00:00:00

  • Pharmacological activity and hydrolysis behavior of novel ibuprofen glucopyranoside conjugates.

    abstract：:Novel ester prodrugs (II, III and IV) of ibuprofen (I) were synthesized using alpha-methyl, ethyl and propyl glucopyranoside as promoieties and tested for their anti-inflammatory, analgesic and ulcerogenic activities. Study of their chemical hydrolysis in aqueous buffer (pH 3.0-10.0) showed that these compounds acted ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2006.05.014

    authors： Zhao X,Tao X,Wei D,Song Q

    更新日期：2006-11-01 00:00:00

  • Synthesis and cancer cell growth inhibitory activity of icaritin derivatives.

    abstract：:A series of icaritin derivatives bearing carboxylic acid or carboxylic ester groups are synthesized, and their in vitro cytotoxic activity against three cancer cell lines, MCF-7, MDA-MB-435s, and A549, are evaluated by MTT assay. Several derivatives including 2h, 2j, 5b and 5d show higher cytotoxic activity than the p...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.06.006

    authors： Wang C,Wu P,Shi JF,Jiang ZH,Wei XY

    更新日期：2015-07-15 00:00:00

  • Discovery of anxiolytic 2-ferrocenyl-1,3-thiazolidin-4-ones exerting GABAA receptor interaction via the benzodiazepine-binding site.

    abstract：:Herein, we report on the synthesis, spectral, crystallographic and electrochemical properties of a small library of N-substituted 2-ferrocenyl-1,3-thiazolidin-4-ones, designed as novel GABAA benzodiazepine-binding site ligands. The anxiolytic properties of the title compounds were evaluated in several different in viv...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.05.062

    authors： Pejović A,Denić MS,Stevanović D,Damljanović I,Vukićević M,Kostova K,Tavlinova-Kirilova M,Randjelović P,Stojanović NM,Bogdanović GA,Blagojević P,D'hooghe M,Radulović NS,Vukićević RD

    更新日期：2014-08-18 00:00:00

  • Design and synthesis of sulfonamide derivatives of pyrrolidine and piperidine as anti-diabetic agents.

    abstract：:Type 2 diabetes (T2D) is a lifestyle disease affecting millions of people worldwide. Various therapies are available for the management of T2D and dipeptidyl peptidase-IV (DPP-IV) inhibition has emerged as a promising therapy for the treatment of type 2 diabetes (T2D). Here we report design, synthesis and in vitro eff...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.11.041

    authors： Sharma R,Soman SS

    更新日期：2015-01-27 00:00:00

  • Caffeoylglycolic and caffeoylamino acid derivatives, halfmers of L-chicoric acid, as new HIV-1 integrase inhibitors.

    abstract：:Human immunodeficiency virus (HIV) integrase (IN) catalyzes the integration of HIV DNA copy into the host cell DNA. L-Chicoric acid (1) has been found to be one of the most potent HIV-1 integrase inhibitor. Caffeoylglycolic and caffeoylamino acid derivatives' halfmeric structures of L-chicoric acid 2 were synthesized ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2007.02.016

    authors： Lee SU,Shin CG,Lee CK,Lee YS

    更新日期：2007-10-01 00:00:00

  • Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors.

    abstract：:A series of pentacyclic triterpene 3β-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.08.012

    authors： Chen D,Huang X,Zhou H,Luo H,Wang P,Chang Y,He X,Ni S,Shen Q,Cao G,Sun H,Wen X,Liu J

    更新日期：2017-10-20 00:00:00

  • Synthesis and study of antiproliferative activity of novel thienopyrimidines on glioblastoma cells.

    abstract：:The receptor tyrosine kinases (for example EGFR, PDGFR, VEGFR) are a transmembrane protein family which plays a crucial role in tumor growth, survival, metastasis dissemination and angiogenesis. During the past 10 years, many tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment (imatinib, gefitini...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.02.032

    authors： Pédeboscq S,Gravier D,Casadebaig F,Hou G,Gissot A,De Giorgi F,Ichas F,Cambar J,Pometan JP

    更新日期：2010-06-01 00:00:00

  • Antimycobacterial activity of natural products and synthetic agents: pyrrolodiquinolines and vermelhotin as anti-tubercular leads against clinical multidrug resistant isolates of Mycobacterium tuberculosis.

    abstract：:Various classes of natural products and synthetic compounds were tested against reference strains and clinical multidrug resistant isolates of Mycobacterium tuberculosis. Vermelhotin (19), a natural tetramic acid from fungi, was the most active toward clinical MDR TB isolates (MIC 1.5-12.5 μg/mL). Synthetic compounds ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.10.026

    authors： Ganihigama DU,Sureram S,Sangher S,Hongmanee P,Aree T,Mahidol C,Ruchirawat S,Kittakoop P

    更新日期：2015-01-07 00:00:00

  • Design, synthesis and anticancer potential of NSC-319745 hydroxamic acid derivatives as DNMT and HDAC inhibitors.

    abstract：:DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important epigenetic targets during anticancer drug development. Recent study indicates that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain cancers, therefore, development of molecules targeting both DNMT and HDAC is of the...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.04.017

    authors： Yuan Z,Sun Q,Li D,Miao S,Chen S,Song L,Gao C,Chen Y,Tan C,Jiang Y

    更新日期：2017-07-07 00:00:00

  • Anti-proliferative evaluation of monoterpene derivatives against leukemia.

    abstract：:The cure rate of pediatric acute lymphoblastic leukemia (ALL) has significantly improved in the past thirty years, however not all patient cohorts respond well to current chemotherapy regimens. Among the high risk patient cohort is infants with MLL-rearranged (MLL-r) B-ALL, which remains dismal with an overall surviva...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.02.034

    authors： Gautam LN,Ling T,Lang W,Rivas F

    更新日期：2016-05-04 00:00:00

  • Synthesis and antioxidant properties of some novel 5H-dibenz[b,f]azepine derivatives in different in vitro model systems.

    abstract：:A series of 5H-dibenz[b,f]azepine containing different aminophenols and substituted aminophenols were synthesized. 3-chloro-1-(5H-dibenz[b,f]azepine-5yl)propan-1-one (2) was obtained by N-acylation of 5H-dibenz[b,f]azepine (1) with 3-chloro propionyl chloride. Further base condensation with different aminophenols and ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.09.016

    authors： Vijay Kumar H,Naik N

    更新日期：2010-01-01 00:00:00