Drug design and synthesis of epsilon opioid receptor agonist: 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception mediated by putative epsilon opioid

Abstract:

:Here we report the new drug design and synthesis of a series of 6,14-endoethenomorphinan-7-carboxamide derivatives as a putative epsilon opioid receptor agonist. One of these compounds, 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821), showed agonistic activity for a putative epsilon opioid receptor (IC(50) = 71.71nM) in the rat vas deferens (RVD) preparations. TAN-821 stimulated the binding of the nonhydrolyzable guanosine 5'-triphosphate analog, guanosine 5'-(gamma-thio)-triphosphate (GTPgammaS), to the mouse pons/medulla membrane via the activation of putative epsilon opioid receptor. Moreover, TAN-821 given intracerebroventricularly (i.c.v.) produced a marked antinociception in the tail-flick test (ED(50) = 1.73 microg) and the hot-plate test (ED(50) = 2.05 microg) in a dose-dependent manner. The antinociception induced by TAN-821 administered i.c.v. was blocked by the i.c.v.-pretreatment with a putative epsilon opioid receptor partial agonist beta-endorphin [1-27], but not a mu opioid receptor antagonist beta-FNA, a delta opioid receptor antagonist NTI, or a kappa opioid receptor antagonist nor-BNI. The present results suggest that TAN-821 may be a useful tool for the investigation on the pharmacological properties of the putative epsilon opioid receptor.

journal_name

Bioorg Med Chem

authors

Fujii H,Narita M,Mizoguchi H,Murachi M,Tanaka T,Kawai K,Tseng LF,Nagase H

doi

10.1016/j.bmc.2004.05.024

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

4133-45

issue

15

eissn

0968-0896

issn

1464-3391

pii

S0968089604003840

journal_volume

12

pub_type

杂志文章
  • Inhibitory activity of Brazilian green propolis components and their derivatives on the release of cys-leukotrienes.

    abstract::The effects of Brazilian green propolis ethanol extract on Cry j1-induced cys-leukotrienes and histamine release from peripheral leukocytes of patients with allergic rhinitis were investigated. One of the key mechanisms for the anti-allergic properties of the extract was revealed to be the suppression of cys-LTs relea...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.11.007

    authors: Tani H,Hasumi K,Tatefuji T,Hashimoto K,Koshino H,Takahashi S

    更新日期:2010-01-01 00:00:00

  • Inactivation of the human papillomavirus-16 E6 oncoprotein by organic disulfides.

    abstract::We are investigating compounds that could be useful in the treatment of neoplastic lesions of the cervix by acting on the oncoprotein E6 of human papillomavirus-16. The E6 protein contains two potential zinc-binding domains that are required for most of its functions. We have published tests that measure (i) the relea...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00193-0

    authors: Beerheide W,Sim MM,Tan YJ,Bernard HU,Ting AE

    更新日期:2000-11-01 00:00:00

  • Effects of detergents on the West Nile virus protease activity.

    abstract::Detergents such as Triton X-100 are often used in drug discovery research to weed out small molecule promiscuous and non-specific inhibitors which act by aggregation in solution and undesirable precipitation in aqueous assay buffers. We evaluated the effects of commonly used detergents, Triton X-100, Tween-20, Nonidet...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.03.050

    authors: Ezgimen MD,Mueller NH,Teramoto T,Padmanabhan R

    更新日期:2009-05-01 00:00:00

  • Solution- and solid-phase synthesis and anti-HIV activity of maslinic acid derivatives containing amino acids and peptides.

    abstract::Maslinic acid (1) has been coupled at C-28 with several alpha- and omega-amino acids by using solution- and solid-phase synthetic procedures. Twelve derivatives (2-13) with a single amino acid residue were prepared in solution phase, whereas a dipeptide (14), a tripeptide (15), and a series of conjugate dipeptides (16...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.12.041

    authors: Parra A,Rivas F,Lopez PE,Garcia-Granados A,Martinez A,Albericio F,Marquez N,Muñoz E

    更新日期:2009-02-01 00:00:00

  • 1,5-Disubstituted 1,2,3-triazoles as cis-restricted analogues of combretastatin A-4: Synthesis, molecular modeling and evaluation as cytotoxic agents and inhibitors of tubulin.

    abstract::A series of cis-restricted 1,5-disubstituted 1,2,3-triazole analogues of combretastatin A-4 (1) have been prepared. The triazole 12f, 2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)aniline, displayed potent cytotoxic activity against several cancer cell lines with IC(50) values in the nanomolar range. T...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.03.049

    authors: Odlo K,Hentzen J,dit Chabert JF,Ducki S,Gani OA,Sylte I,Skrede M,Flørenes VA,Hansen TV

    更新日期:2008-05-01 00:00:00

  • Anti-inflammatory properties of a heparin-like glycosaminoglycan with reduced anti-coagulant activity isolated from a marine shrimp.

    abstract::The anti-inflammatory properties of a heparin-like compound from the shrimp Litopenaeus vannamei are related. Besides reducing significantly (p<0.001) the influx of inflammatory cells to injury site in a model of acute inflammation, shrimp heparin-like compound was able to reduce the matrix metalloproteinase (MMPs) ac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.09.020

    authors: Brito AS,Arimatéia DS,Souza LR,Lima MA,Santos VO,Medeiros VP,Ferreira PA,Silva RA,Ferreira CV,Justo GZ,Leite EL,Andrade GP,Oliveira FW,Nader HB,Chavante SF

    更新日期:2008-11-01 00:00:00

  • Stereoselective preparation of pyridoxal 1,2,3,4-tetrahydro-β-carboline derivatives and the influence of their absolute and relative configuration on the proliferation of the malaria parasite Plasmodium falciparum.

    abstract::We have selectively synthesized by Pictet-Spengler condensation of tryptophan and pyridoxal the four stereoisomers of a pyridoxal β-carboline derivative that was designed to inhibit the proliferation of Plasmodium falciparum. Biological investigation of the four compounds revealed that they all inhibit the growth of P...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.01.057

    authors: Brokamp R,Bergmann B,Müller IB,Bienz S

    更新日期:2014-03-15 00:00:00

  • Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors.

    abstract::Therapeutic development of a targeted agent involves a series of decisions over additional activities that may be ignored, eliminated or pursued. This paper details the concurrent application of two methods that provide a spectrum of information about the biological activity of a compound: biochemical profiling on a l...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.10.090

    authors: Ross-Macdonald P,de Silva H,Patel V,Truong A,He A,Neuhaus I,Tilford C,Ji R,Siemers N,Greer A,Carboni J,Gottardis M,Menard K,Lee F,Dodier M,Frennesson D,Sampognaro A,Saulnier M,Trainor G,Vyas D,Zimmermann K,Wittm

    更新日期:2012-03-15 00:00:00

  • Synthesis of novel 7-oxo and 7-hydroxy trifluoroallocolchicinoids with cytotoxic effect.

    abstract::The synthesis of 7-oxo and 7-hydroxy trifluoroallocolchicinoids was achieved through the intramolecular cyclization of o-phenyl-β-phenylalanines. The resulting compounds were evaluated for their cytotoxic activity against KB cells and their inhibitory effect towards the polymerization of tubulin. The results yielded s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.02.043

    authors: Chosson E,Santoro F,Rochais C,Santos JS,Legay R,Thoret S,Cresteil T,Sinicropi MS,Besson T,Dallemagne P

    更新日期:2012-04-15 00:00:00

  • Actin-binding doliculide causes premature senescence in p53 wild type cells.

    abstract::Addressing the actin cytoskeleton as future anticancer target can be an innovative chemotherapeutic approach to combat malignancies. Doliculide is a potent stabilizer of actin filaments and can be used as tool and therapeutic lead in cancer research. Though a variety of molecules are known to bind to actin and lead to...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.11.042

    authors: Foerster F,Chen T,Altmann KH,Vollmar AM

    更新日期:2016-01-15 00:00:00

  • Heteroarylamide smoothened inhibitors: Discovery of N-[2,4-dimethyl-5-(1-methylimidazol-4-yl)phenyl]-4-(2-pyridylmethoxy)benzamide (AZD8542) and N-[5-(1H-imidazol-2-yl)-2,4-dimethyl-phenyl]-4-(2- pyridylmethoxy)benzamide (AZD7254).

    abstract::Aberrant hedgehog (Hh) pathway signaling is implicated in multiple cancer types and targeting the Smoothened (SMO) receptor, a key protein of the Hh pathway, has proven effective in treating metastasized basal cell carcinoma. Our lead optimization effort focused on a series of heteroarylamides. We observed that a meth...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.115227

    authors: Yang B,Hird AW,Bodnarchuk MS,Zheng X,Dakin L,Su Q,Daly K,Godin R,Hattersley MM,Brassil P,Redmond S,John Russell D,Janetka JW

    更新日期:2020-01-15 00:00:00

  • A conformational transition in the adenylyl cyclase catalytic site yields different binding modes for ribosyl-modified and unmodified nucleotide inhibitors.

    abstract::Adenylyl cyclases (ACs) are promising pharmacological targets for treating heart failure, cancer, and psychosis. Ribose-substituted nucleotides have been reported as a potent family of AC inhibitors. In silico analysis of the docked conformers of such nucleotides in AC permits assembly of a consistent, intuitive QSAR ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.02.014

    authors: Wang JL,Guo JX,Zhang QY,Wu JJ,Seifert R,Lushington GH

    更新日期:2007-04-15 00:00:00

  • Novel curcumin analogs to overcome EGFR-TKI lung adenocarcinoma drug resistance and reduce EGFR-TKI-induced GI adverse effects.

    abstract::Curcumin (1) down-regulates the expression as well as phosphorylation of epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells expressing gefitinib-resistant EGFR. Thirty-seven newly synthesized curcumin analogues including dimethoxycurcumin (2, DMC) were evaluated for their effects on EGFR expression a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.02.003

    authors: Wada K,Lee JY,Hung HY,Shi Q,Lin L,Zhao Y,Goto M,Yang PC,Kuo SC,Chen HW,Lee KH

    更新日期:2015-04-01 00:00:00

  • Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease.

    abstract::Canavan disease is a fatal neurological disorder caused by defects in the metabolism of N-acetyl-l-aspartate (NAA). Recent work has shown that the devastating symptoms of this disorder are correlated with the elevated levels of NAA observed in these patients, caused as a consequence of the inability of mutated forms o...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.11.060

    authors: Thangavelu B,Mutthamsetty V,Wang Q,Viola RE

    更新日期:2017-02-01 00:00:00

  • Synthesis, cellular internalization and photodynamic activity of glucoconjugated derivatives of tri and tetra(meta-hydroxyphenyl)chlorins.

    abstract::Glucoconjugated tri and tetra(meta-hydroxyphenyl)chlorins have been synthesized in order to explore how glucoconjugation of the macrocycle affects the photoactivity of the molecule. Internalization processes, photosensitizing efficacy of TPC(m-O-GluOH)(3) and TPC(m-O-GluOH)(4), in HT29 human adenocarcinoma cells have ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(03)00050-6

    authors: Laville I,Figueiredo T,Loock B,Pigaglio S,Maillard P,Grierson DS,Carrez D,Croisy A,Blais J

    更新日期:2003-04-17 00:00:00

  • Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds.

    abstract::Use of herbal plant remedies to treat infectious diseases is a common practice in many countries in traditional and alternative medicine. However to date there are only few antimicrobial agents derived from botanics. Based on microbiological screening tests of crude plant extracts we identified four compounds derived ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.11.052

    authors: Artini M,Papa R,Barbato G,Scoarughi GL,Cellini A,Morazzoni P,Bombardelli E,Selan L

    更新日期:2012-01-15 00:00:00

  • Design, synthesis and bioactivities of Celecoxib analogues or derivatives.

    abstract::A series of Celecoxib analogues or derivatives were designed and synthesized, and their biological activities were studied. The results of inhibitory activity in vitro proved that compounds 1a, 1h, 1i, 1l and 1p had better inhibitory effect on COX-2, and the selectivity was higher. Among them, the inhibitory activity ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.07.038

    authors: Zhou S,Yang S,Huang G

    更新日期:2017-09-01 00:00:00

  • 11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents.

    abstract::Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy deriv...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.08.018

    authors: Feng W,Satyanarayana M,Tsai YC,Liu AA,Liu LF,LaVoie EJ

    更新日期:2008-09-15 00:00:00

  • Identification of topoisomerases as molecular targets of cytosporolide C and its analog.

    abstract::Cytosporolide (Cytos) A-C, isolated from the fungus Cytospora sp., have anti-microbial activity, but their molecular targets in mammalian cells are unknown. We have previously reported the total synthesis of Cytos A by biomimetic hetero-Diels-Alder reaction. In this study, to examine the novel bioactivity of Cytos, we...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.06.014

    authors: Otake K,Yamada K,Miura K,Sasazawa Y,Miyazaki S,Niwa Y,Ogura A,Takao KI,Simizu S

    更新日期:2019-08-01 00:00:00

  • Synthesis and evaluation of N-substituted nipecotic acid derivatives with an unsymmetrical bis-aromatic residue attached to a vinyl ether spacer as potential GABA uptake inhibitors.

    abstract::γ-Amino butyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system (CNS). A malfunction of the GABAergic neurotransmission is connected to several neuronal disorders like epilepsy, Alzheimer's disease, neuropathic pain, and depression. One possibility to enhance GABA levels in...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.02.056

    authors: Quandt G,Höfner G,Wanner KT

    更新日期:2013-06-01 00:00:00

  • A novel library of saccharin and acesulfame derivatives as potent and selective inhibitors of carbonic anhydrase IX and XII isoforms.

    abstract::Small libraries of N-substituted saccharin and N-/O-substituted acesulfame derivatives were synthesized and tested as atypical and selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). Most of them inhibited hCA XII in the low nanomolar range, hCA IX with KIs ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.01.038

    authors: Carradori S,Secci D,De Monte C,Mollica A,Ceruso M,Akdemir A,Sobolev AP,Codispoti R,De Cosmi F,Guglielmi P,Supuran CT

    更新日期:2016-03-01 00:00:00

  • CC-1065 CBI analogs: an example of enhancement of DNA alkylation efficiency through introduction of stabilizing electrostatic interactions.

    abstract::The three trimethylammonium salts 3-5 proved to be 100 times more efficient at alkylating DNA than 2 and exhibited DNA alkylation efficiencies identical to that of (+)-CC-1065 (1). In addition, the agents 3 and 4 exhibited DNA alkylation selectivities identical to that of 2. This may be attributed to spatially well-de...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(95)00048-l

    authors: Boger DL,Yun W,Han N,Johnson DS

    更新日期:1995-06-01 00:00:00

  • 5-Nitro-2-furfuriliden derivatives as potential anti-Trypanosoma cruzi agents: design, synthesis, bioactivity evaluation, cytotoxicity and exploratory data analysis.

    abstract::The anti-Trypanosoma cruzi activity of 5-nitro-2-furfuriliden derivatives as well as the cytotoxicity of these compounds on J774 macrophages cell line and FN1 human fibroblast cells were investigated in this study. The most active compounds of series I and II were 4-butyl-[N'-(5-nitrofuran-2-yl) methylene] benzidrazid...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.06.017

    authors: Palace-Berl F,Jorge SD,Pasqualoto KF,Ferreira AK,Maria DA,Zorzi RR,de Sá Bortolozzo L,Lindoso JÂ,Tavares LC

    更新日期:2013-09-01 00:00:00

  • Novel epidithiodiketopiperazines as anti-viral zinc ejectors of the Feline Immunodeficiency Virus (FIV) nucleocapsid protein as a model for HIV infection.

    abstract::Focused libraries of multi-substituted epidithiodiketopiperazines (ETP) were prepared and evaluated for efficacy of inhibiting the nucleocapsid protein function of the Feline Immunodeficiency Virus (FIV) as a model for HIV. This activity was compared and contrasted to observed toxicity utilising an in-vitro cell cultu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.07.047

    authors: Asquith CRM,Sil BC,Laitinen T,Tizzard GJ,Coles SJ,Poso A,Hofmann-Lehmann R,Hilton ST

    更新日期:2019-09-15 00:00:00

  • Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

    abstract::We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.05.035

    authors: Tsuji T,Suzuki K,Nakamura T,Goto T,Sekiguchi Y,Ikeda T,Fukuda T,Takemoto T,Mizuno Y,Kimura T,Kawase Y,Nara F,Kagari T,Shimozato T,Yahara C,Inaba S,Honda T,Izumi T,Tamura M,Nishi T

    更新日期:2014-08-01 00:00:00

  • Formylchromone derivatives as irreversible and selective inhibitors of human protein tyrosine phosphatase 1B. Kinetic and modeling studies.

    abstract::A series of formylchromone derivatives were synthesized as PTP1B inhibitors and some of them were potent against PTP1B with IC50 values as low as 1.0 microM. They exhibited remarkable selectivity for PTP1B over other human PTPases. Kinetic studies revealed that formylchromone derivatives are irreversible and active si...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.11.006

    authors: Shim YS,Kim KC,Lee KA,Shrestha S,Lee KH,Kim CK,Cho H

    更新日期:2005-02-15 00:00:00

  • The case for configurational stability of H-phosphonate diesters in the presence of diazabicyclo[5.4.0]undec-7-ene (DBU).

    abstract::Configurational stability of dinucleoside H-phosphonates and the stereochemical course of their sulfurisation in the presence of diazabicyclo[5.4.0]undec-7-ene (DBU) were investigated using 31P NMR spectroscopy. It was found that under the reaction conditions and irrespective of the type of protecting groups present i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(01)00140-7

    authors: Johansson T,Stawinski J

    更新日期:2001-09-01 00:00:00

  • Promising anti-growth effects of palladium(II) saccharinate complex of terpyridine by inducing apoptosis on transformed fibroblasts in vitro.

    abstract::Fibrosarcoma is one of the fatal cancer types and there is still not satisfactory success in its treatment despite new drugs. Therefore, the search for a new compound has been going on. It is currently known that some palladium-based anti-cancer compounds seem to have powerful apoptosis-inducing effects in cancer cell...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.05.023

    authors: Coskun MD,Ari F,Oral AY,Sarimahmut M,Kutlu HM,Yilmaz VT,Ulukaya E

    更新日期:2013-08-01 00:00:00

  • Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana.

    abstract::A series of hydroxyalkyl and acyloxyalkyl derivatives of 2- and 3-hydroxypyridine was synthesized and their biological activity was evaluated as growth inhibitors of protozoan Leishmania mexicana. Thirty novel compounds were obtained through a chemoenzymatic methodology in two reaction steps. The influence of various ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.06.028

    authors: García Liñares G,Parraud G,Labriola C,Baldessari A

    更新日期:2012-08-01 00:00:00

  • A novel molecular modelling study of inhibitors of the 17alpha-hydroxylase component of the enzyme system 17alpha-hydroxylase/17,20-lyase (P-450(17alpha)).

    abstract::The enzyme 17alpha-hydroxylase/17,20-lyase (P-450(17alpha) has recently become the focus of research into the fight against hormone dependent prostate cancer. However, the specific nature of this enzyme, in particular, the dual role of its active site, remains unknown. In our drive to elucidate further information reg...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(99)00077-2

    authors: Ahmed S

    更新日期:1999-08-01 00:00:00