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1.
Chin J Nat Med ; 15(5): 347-354, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28558870

RESUMO

The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13ß, 28-olide (1), a lactone derivative of oleanolic acid (OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide (NO) production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1ß, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury (ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase (MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Ácido Oleanólico/administração & dosagem , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/imunologia , Animais , Anti-Inflamatórios/síntese química , Líquido da Lavagem Broncoalveolar/imunologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/síntese química , Peroxidase/genética , Peroxidase/imunologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
2.
Int J Ophthalmol ; 3(1): 9-13, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-22553508

RESUMO

AIM: To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells (ARPE-19). METHODS: Human retinal pigmented epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth, and their mechanisms of proliferative action by using ERK, AKT, PI3K, Protein kinase C (PKC) and Nitric oxide synthase (NOS) inhibitors. RESULTS: (R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation, but not on HUVECs. When treated with proliferative inhibitors, H-7 (5µmol/L), hypericin (20µmol/L), PD98059 (2µmol/L), LY294002 (50µmol/L), SH-5 (10µmol/L) and L-NAME (100µmol/L), the proliferative effect was reduced by H-7, hypericin, PD98059 and LY294002, but not by SH-5 and L-NAME. CONCLUSION: (R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway.

3.
Chem Biodivers ; 6(4): 466-74, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19353543

RESUMO

In search of more potent anticancer agents, 15 nitric oxide (NO)-donating thalidomide analogues, 6a, 6b, 8a-8e, and 13a-13h, were designed and synthesized. Cytotoxicity of these compounds was evaluated in vitro against three human tumor cell lines (HepG2, A549, and PC-3). The results indicated that 13a-13d exhibited notable anticancer activities comparable to or stronger than that of 5-fluorouracil (5-FU). Structure-activity relationships were also discussed, based on the experimental data obtained. Generally, the cytotoxic activity of target compounds is closely related to the type of NO donors, and the length of the spacers connecting to NO donors also appears important for the bioactivities.


Assuntos
Antineoplásicos/síntese química , Óxido Nítrico/química , Talidomida/análogos & derivados , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Fluoruracila/toxicidade , Humanos , Talidomida/toxicidade
4.
Yao Xue Xue Bao ; 44(11): 1200-10, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-21355319

RESUMO

Nitric oxide (NO) as a messenger and/or effector plays important roles in vivo. The decreased availability of NO or dysfunction in NO signaling has often been implicated in the development and progression of diseases, and design and research of NO-donating drugs has become one of the important strategies in drug discovery. In connection with authors' scientific practice, this article reviews the recent advances in the research of NO-donating drugs.


Assuntos
Antineoplásicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Aspirina/análogos & derivados , Aspirina/farmacologia , Aspirina/uso terapêutico , Compostos Azo/farmacologia , Linhagem Celular Tumoral , Desenho de Fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nitratos/farmacologia , Nitratos/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Piperazinas/farmacologia , Transdução de Sinais/efeitos dos fármacos
5.
Chem Biodivers ; 5(9): 1743-52, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18816527

RESUMO

In search of novel anticancer agents, two series of dimethyl [1,1'-biphenyl]-2,2'-dicarboxylate derivatives, 8a-8k and 9a-9k, containing both methylenedioxy and 1,3,4-thiadiazole moieties were designed and synthesized. Cytotoxicity of these compounds was evaluated in vitro against five human tumor cell lines, i.e., HepG2, KB, A549, K562, and MCF-7. The results indicated that 8h, 8j, 8k, 9d, 9g, 9h, 9j, and 9k showed notable anticancer activities comparable to or stronger than that of 5-fluorouracil, a canonical anticancer drug. Structure-activity relationships were also discussed based on the experimental data obtained.


Assuntos
Compostos de Bifenilo/síntese química , Compostos de Bifenilo/toxicidade , Tiadiazóis/química , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Metilação , Estrutura Molecular , Relação Estrutura-Atividade
6.
Yao Xue Xue Bao ; 42(4): 352-7, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17633199

RESUMO

Traditional non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors are among the most widely used drugs. However, their significant side effects in gastrointestinal and cardiovascular systems limited the use of these drugs. Recently, research and development of NO-donating NSAIDs (NO-NSAIDs) have become one of the most important strategies to reduce these side effects. NO-NSAIDs may exert a broad range of positive effects in terms of NO-mediated gastrointestinal and cardiovascular safety as well as comparable or increased anti-inflammatory, analgesic properties relative to NSAIDs. This review briefly deals with chemistry of NO-NSAIDs, more details are focused on biological significance, mechanism of action, and therapeutic potential of this novel class of drugs.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Doadores de Óxido Nítrico/farmacologia , Acetaminofen/análogos & derivados , Acetaminofen/química , Acetaminofen/farmacologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/análogos & derivados , Aspirina/química , Aspirina/farmacologia , Cardiotônicos/farmacologia , Inibidores de Ciclo-Oxigenase/efeitos adversos , Inibidores de Ciclo-Oxigenase/farmacologia , Flurbiprofeno/análogos & derivados , Flurbiprofeno/química , Flurbiprofeno/farmacologia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/prevenção & controle , Humanos , Ibuprofeno/análogos & derivados , Ibuprofeno/química , Ibuprofeno/farmacologia , Naproxeno/análogos & derivados , Naproxeno/química , Naproxeno/farmacologia , Nitratos/química , Nitratos/farmacologia
8.
Yao Xue Xue Bao ; 41(11): 1050-6, 2006 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-17262946

RESUMO

AIM: To synthesize and study the antithrombotic activity of NO-donating aspirin derivatives. METHODS: Furoxans and nitrates were incorporated to aspirin via antioxidant ferulic acid as a linker, and the target compounds were screened for in vitro and in vivo inhibitory activities of platelet aggregation, and for inhibitory effect on A-V hypass thromhosis in rats. RESULTS: Fourteen novel compounds I(1-14), were synthesized and their structures were confirmed Iy MS, IR, 1H NMR and elemental analysis. Biological screening results demonstrated that some tested compounds exhibited potential antithrombotic activ it. CONCLUSION: Acetylsalicyl ferulic acid-coupling furoxans and nitrates might he used as a lead for further study.


Assuntos
Aspirina/química , Ácidos Cumáricos/química , Fibrinolíticos/síntese química , Nitratos/química , Oxidiazóis/química , Animais , Fibrinolíticos/química , Fibrinolíticos/farmacologia , Modelos Químicos , Estrutura Molecular , Doadores de Óxido Nítrico/química , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Ratos
9.
Yao Xue Xue Bao ; 39(7): 546-50, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15493848

RESUMO

AIM: To study the structure and crystal forms of chlorobenzylidine. METHODS: Karl Fischer titrimetry, FTIR, thermal analysis, single and powder X-ray diffraction were used for the studies of the structure of chlorobenzylidine and for the identification of two forms of chlorobenzylidine. RESULTS: Chlorobenzylidine and its diastereoisomer have been studied in this article. They can be distinguished by their different melting points. Two crystal forms of chlorobenzylidine (form A and form B) have also been detected and studied. Form A was studied by single-crystal X-ray diffraction, it crystallized in the triclinic system, space group P1(-), with two formula units per cell, is monohydrate. Karl Fischer titrimetry, FTIR, thermal analysis and powder X-ray diffraction were used for identification of the two forms. CONCLUSION: The studies of structure and crystal forms of chlorobenzylidine are very useful for the clinical research and the selection of recrystallization process.


Assuntos
Compostos Policíclicos/química , Compostos de Benzilideno , Cristalização , Cristalografia por Raios X , Análise Diferencial Térmica , Conformação Molecular , Estrutura Molecular , Estereoisomerismo
10.
Yao Xue Xue Bao ; 38(6): 442-7, 2003 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-14513805

RESUMO

AIM: In order to look for new bioactive compounds, investigation on the chemical constituents, especially on the typical polyacetylenes from the rhizomes of Cirsium japonicum DC. was carried out. METHODS: Chromatographic techniques including silica column chromatography and preparative silica thin-layer chromatography were used to separate and purify the constituents. Their structures were elucidated by physicochemical properties and spectral analyses including UV, IR, 1HNMR, 13CNMR, HMQC, HMBC and HREIMS. RESULTS: Twelve compounds were isolated from the rhizomes of Cirsium japonicum DC., and their structures were identified as cis-8, 9-epoxy-heptadeca-1-ene-11, 13-diyne-10-ol (1), ciryneol A (2), 8,9,10-triacetoxyheptadeca-1-ene-11,13-diyne (3), ciryneone F (4), cireneol G (5), ciryneol H (6), ciryneol C (7), p-coumaric acid (8), syringin (9), linarin (10), beta-sitosterol (11) and daucosterol (12). CONCLUSION: Compounds 4, 5 and 6 are new compounds, compound 3 is a new natural product and compound 8 was isolated from this plant for the first time.


Assuntos
Cirsium/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Plantas Medicinais/química , Medicamentos de Ervas Chinesas/química , Conformação Molecular , Estrutura Molecular , Rizoma/química
11.
J Ocul Pharmacol Ther ; 19(3): 247-53, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12828842

RESUMO

PURPOSE: To invent a drug which can specifically facilitate choroid blood flow via increase of nitric oxide (NO). METHOD: Cell culture was used for in vitro experiments to determine the production of NO by NO donors and colored microsphere technique was used for in vivo experiments to determine the blood flow in various tissues of rabbit eyes. RESULTS: ZX-5 and ZX-4 are two geographic isomers with ZX-5 as trans-form and ZX-4 as cis-form. (1-phenyl-3-[3-methoxy-2-propoxy-5-[4-(3,4,5-trimethoxy-phenyl)-1,3-d lane-2-yl]phenyl]thiourea). It was found that ZX-5 released significant amount of NO at 3, 10, 30 microg/ml concentrations and increased choroid blood flow at 1%, 50 microl instillation into eyes. It was not effective on the blood flow of iris or ciliary body. The corresponding ZX-4 was not effective on ocular blood flow nor it released NO. CONCLUSION: ZX-5 can specifically increase the choroidal blood flow which could be useful to suppress the choroidal neovascularization in age-related macular degeneration (AMD). It is hoped that ZX-5 type of compounds could be used for the treatment/prevention of AMD in the elderly.


Assuntos
Corioide/efeitos dos fármacos , Óxido Nítrico/biossíntese , Tioureia/farmacologia , Animais , Células Cultivadas , Corioide/irrigação sanguínea , Corpo Ciliar/irrigação sanguínea , Técnicas In Vitro , Iris/irrigação sanguínea , Hipertensão Ocular/fisiopatologia , Coelhos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Estereoisomerismo , Tioureia/análogos & derivados , Tioureia/química
12.
Yao Xue Xue Bao ; 37(1): 27-32, 2002 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-12579895

RESUMO

AIM: To search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects. METHODS: Coupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo. RESULTS: Fifteen new compounds including nine target ones (II1-9) were synthesized, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compounds II3 and II9 showed anti-inflammatory activity comparable to DC. Compound II2 showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo. CONCLUSION: Compound II2 is worthy to be intensively studied.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Diclofenaco/síntese química , Analgésicos/síntese química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Óxidos N-Cíclicos/administração & dosagem , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacologia , Diclofenaco/farmacologia , Diclofenaco/uso terapêutico , Sistema Digestório/efeitos dos fármacos , Edema/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia , Oxidiazóis/administração & dosagem , Oxidiazóis/química , Oxidiazóis/farmacologia , Limiar da Dor/efeitos dos fármacos , Ratos , Relação Estrutura-Atividade
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