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1.
Eur J Med Chem ; 178: 484-499, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31202994

RESUMO

In our work, 19 novel 4,5-diazafluorene derivatives (11a-d, 12a-d, 13a-d, 14a-c, 15c, 16a-c) bearing a 1,3-disubstituted pyrazol/thioxothiazolidinone or thioxothiazolidinone-oxadiazole moieties were designed, synthesized, preliminarily explored for their antitumor activities and in vitro mechanism. All compounds showed different values of antiproliferative activity against A549, AGS, HepG2 and MCF-7 cell lines through CCK-8. Especially, the compound 14c exhibited the strongest activity and best selectivity against A549 cells with an IC50 1.13 µM and an SI value of 7.01 relative to MRC-5 cells, which was better than cisplatin (SI = 1.80) as a positive control. Experimental results at extracellular level demonstrated that compounds 14a-c could strongly interact with the G-quadruplex(es) formed in a 26 nt telomeric G-rich DNA, in particular, the 14c exhibits quite strong binding affinity with an association equilibrium constant (KA) of 7.04(±0.16) × 107 M-1 and more than 1000-fold specificity to G4-DNA over ds-DNA and Mut-DNA at the compound/G4-DNA ratio of 1:1. Further trap assay ascertained that compounds 14a-c owned strong inhibitory ability of telomerase activity in A549 cells, suggesting that these compounds have great possibility to target telomeric G-quadruplexes and consequently indirectly inhibit the telomerase activity. In addition, it is worthy of note that the remarkable inhibitory effects of 14a-c on the mobility of tested cancer cells were observed by wound healing assays. Furthermore, molecular docking and UV-Vis spectral results unclose the rationale for the interaction of compounds with such G-quadruplex(es). These results indicate that the growth and metastasis inhibition of cancer cells mediated by these 4,5-diazafluorene derivatives possibly result from their interaction with telomeric G-quadruplexes, suggesting that 4,5-diazafluorene derivatives, especially 14c, possess potential as anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Desenho de Drogas , Fluorenos/farmacologia , Quadruplex G/efeitos dos fármacos , Telômero/efeitos dos fármacos , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fluorenos/síntese química , Fluorenos/química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Cicatrização/efeitos dos fármacos
2.
Mini Rev Med Chem ; 19(18): 1517-1530, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30864519

RESUMO

At present, cancers have been causing deadly fears to humans and previously unpredictable losses to health. Especially, lung cancer is one of the most common causes of cancer-related mortality accounting for approximately 15% of all cancer cases worldwide. While Non-Small Cell Lung Carcinomas (NSCLCs) makes up to 80% of lung cancer cases. The patient compliance has been weakening because of serious drug resistance and adverse drug effects. Therefore, there is an urgent need for the development of novel structural agents to inhibit NSCLCs. Nitrogen-containing heterocyclic compounds exhibit wide range of biological properties, especially antitumor activity. We reviewed some deadly defects of clinical medicines for the lung cancer therapy and importance of nitrogen based heterocyclic derivatives against NSCLCs. Nitrogen heterocycles exhibit significant antitumor activity against NSCLCs. Nitrogen heterocyclic hybrids could be developed as multi-target-directed NSCLC inhibitors and it is believed that the review is significant for rational designs and new ideas in the development of nitrogen heterocyclic-based drugs.


Assuntos
Antineoplásicos/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Compostos Heterocíclicos/química , Neoplasias Pulmonares/tratamento farmacológico , Nitrogênio/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Azóis/química , Azóis/farmacologia , Azóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Piridinas/química , Piridinas/farmacologia , Piridinas/uso terapêutico
3.
Mini Rev Med Chem ; 18(11): 948-961, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27697041

RESUMO

At present, diseases resulting from various reasons have been causing deadly fears to humans and previously incogitable losses to health. Meanwhile, the patient compliance has been weakening because of drug resistance and serious drug adverse effects. There is therefore an urgent need for the development of novel structural agents. Rhodanine derivatives have exhibited wide biological activities, as well as significant industrial applications, which suggests that rhodanine heterocycle represents a key structural motif in heterocyclic chemistry and occupies a prominent position in drug discovery. Here, we review some deadly defects of clinical medicines to the therapy of diseases and important advances on rhodanine derivatives in drug researches (e.g. as anti-diabetic, anti-viral, antiinflammatory, anti-microbial, anti-tumor agents and inhibitors for Alzheimer Disease), indicating that rhodanine heterocycle could be used as a significant pharmacophore to develop novel pharmacological active molecules. It is believed that the review is of importance for new ideas in the development of and rational designs of rhodanine-based drugs.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Hipoglicemiantes/farmacologia , Neoplasias/tratamento farmacológico , Rodanina/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antineoplásicos/síntese química , Antineoplásicos/química , Diabetes Mellitus/tratamento farmacológico , Desenho de Drogas , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Rodanina/síntese química , Rodanina/química
4.
World Neurosurg ; 105: 709-713, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28642174

RESUMO

OBJECTIVES: The objectives of this study were to examine the correlation between the level of serum inflammatory markers and the stability of carotid plaques in patients with ischemic cerebrovascular disease and to assess the ability of each inflammatory marker to identify vulnerable carotid plaques. METHODS: For the early identification of vulnerable carotid plaques, 65 patients with carotid plaques were divided into a stable plaque group (n = 21) and an unstable plaque group (n = 44) according to magnetic resonance imaging characteristics. The unstable plaque group was divided into an unstable unruptured plaque group (n = 29) and an unstable ruptured plaque group (n = 15) according to whether the fibrous cap was ruptured. The levels of serum soluble cluster of differentiation 40 ligand (sCD40L), matrix metalloproteinase (MMP)-9, and MMP-2 were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of serum sCD40L and MMP-9 in the unstable plaque group, the unstable unruptured plaque group and the ruptured plaque group were significantly higher than those in the stable plaque group (P < 0.05). There was no significant difference in the MMP-2 level between the stable plaque group and unstable plaque group (P = 0.056). The MMP-2 levels in the stable plaque group, unstable unruptured plaque group, and ruptured plaque group were not different (P = 0.095). The carotid plaques and the positive rate of MMP-9 of ≥84.09 ng/mL were statistically significant, suggesting increased vulnerability. CONCLUSIONS: Serum levels of sCD40L and MMP-9 are associated with the stability of carotid plaques. Higher levels of serum sCD40L and MMP-9 may suggest that the plaques are vulnerable or have ruptured.


Assuntos
Isquemia Encefálica/sangue , Ligante de CD40/sangue , Doenças das Artérias Carótidas/sangue , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão
5.
Eur J Med Chem ; 133: 36-49, 2017 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-28376371

RESUMO

A novel series of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines were designed, synthesized and evaluated for their antitumor activity against lung adenocarcinoma by CCK-8 assay, electrophoretic mobility shift assay (EMSA), UV-melting study, wound healing assay and docking study. These compounds showed good inhibitory activities against lung adenocarcinoma. Especially compound 12c exhibited potential antiproliferative activity against A549 cell line with the half maximal inhibitory concentration (IC50) value of 1.48 µM, which was a more potent inhibitor than cisplatin (IC50 = 12.08 µM) and leading compound 2 (IC50 = 1.69 µM), and the maximum cell inhibitory rate being up to 98.40%. Moreover, further experiments demonstrated that compounds 12a-d can strongly interact with telomeric DNA to stabilize G-quadruplex DNA with increased ΔTm values from 12.44 to 20.54 °C at a ratio of DNA to compound 1:10. These results implied that growth inhibition of A549 cells mediated by these phenanthroline derivatives is possibly positively correlated to the fact their interaction with telomeric G-quadruplexs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Pulmão/efeitos dos fármacos , Fenantrolinas/química , Fenantrolinas/farmacologia , Células A549 , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Quadruplex G/efeitos dos fármacos , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fenantrolinas/síntese química , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacologia , Telômero/efeitos dos fármacos , Telômero/genética , Telômero/patologia
6.
J Clin Neurosci ; 34: 202-206, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27658574

RESUMO

This study reports our experience of balloon-in-stent assisted coiling for the treatment of morphologically unfavorable aneurysms located in the internal carotid artery (ICA). From July 2007 to April 2014, twelve patients with twelve aneurysms located in the ICA were coil embolized by simultaneously using balloon and stent assistance. Five aneurysms were ruptured and seven were unruptured. All the aneurysms were overwide (dome-to-neck ratio ⩽1.2) and undertall (aspect ratio ⩽1.2) anatomically. The procedure-related adverse events, clinical and angiographic results were retrospectively analyzed. Intraprocedural aneurysmal bleeding occurred for one unruptured aneurysm but was stopped immediately after the balloon was inflated. Periprocedural thromboembolism occurred for two ruptured aneurysms, leading to death in one patient and severe neurological deficit for the other one. Procedure-related permanent morbidity and mortality rates were 8.3% (1/12) and 8.3% (1/12). Satisfactory (total and subtotal) occlusion was obtained immediately in 11 (91.7%) cases. Nine aneurysms received digital subtraction angiography follow-up (mean 25.1months, range 6-55), and all of them except one were totally obliterated. No aneurysmal bleeding occurred during a mean period of 59.1months, clinical follow-up for eleven patients. Balloon-in-stent assisted coiling might be a therapeutic alternative to prevent growth or rupture of overwide and undertall aneurysms. Nevertheless, it should be used prudently for ruptured ICA aneurysms, for its disadvantage of technical complexity and relatively high rate of adverse events.


Assuntos
Oclusão com Balão/métodos , Aneurisma Intracraniano/terapia , Stents , Adulto , Idoso , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Angiografia Digital , Dissecação da Artéria Carótida Interna/complicações , Dissecação da Artéria Carótida Interna/diagnóstico por imagem , Dissecação da Artéria Carótida Interna/terapia , Angiografia Cerebral , Embolização Terapêutica , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia/complicações , Tromboembolia/diagnóstico por imagem , Resultado do Tratamento
7.
Med Chem ; 12(8): 751-759, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27550428

RESUMO

BACKGROUND: An alarming increment in pathogenic resistance to existing anti-microbial agents is a serious problem and the treatment of these bacterial infections is becoming increasingly challenging. Therefore, there is an urgent need to develop novel antimicrobial agents. OBJECTIVE: As a part of our ongoing studies toward the development of novel antibacterial agents, the synthesis and antibacterial activity of a series of (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives will be discussed in this study. METHOD: (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives were designed, synthesized and evaluated for antibacterial activity. The structures were confirmed by IR, 1H NMR, 13C NMR and mass spectrometry. All of the synthesized compounds were evaluated in vitro using a 96-well microtiter plate and a serial dilution method to obtain their minimum inhibitory concentration (MIC) values against a variety of different strains, including multidrug-resistant clinical isolates. RESULTS: The antibacterial test in-vitro showed that most compounds in series 7 and 9 exhibited significant inhibitory activities against anaerobic bacteria (Streptococcus mutans) strains with a MIC value of 1 µg/mL. Compounds 7c and 9c showed the most potent activity against MRSA (3167 and 3506) with a minimum inhibitory concentration (MIC) value of 1 µg/mL, which is equivalent to moxifloxacin and greater than gatifloxacin, oxacillin and norfloxacin. Additionally, compound 9c showed potent antibacterial activity against Bacillus subtilis (aerobic bacteria) with a MIC value of 2 µg/mL. CONCLUSION: The work suggests that these type of rhodanine compounds had a better potent activity against MRSA compared with other perviously reported rhodanine derivatives, which might provide a valuable information for the development of new antibacterial agents against multidrug-resistant clinical isolates MRSA.


Assuntos
Antibacterianos/farmacologia , Pirazóis/farmacologia , Tioidantoínas/farmacologia , Antibacterianos/síntese química , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas/farmacologia , Gatifloxacina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Moxifloxacina , Norfloxacino/farmacologia , Oxacilina/farmacologia , Pirazóis/síntese química , Estereoisomerismo , Streptococcus mutans/efeitos dos fármacos , Tioidantoínas/síntese química
8.
Biomed Res Int ; 2016: 2428970, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27195283

RESUMO

Background. Whether carotid tortuosity/kinking of the internal carotid artery leads to cerebral ischemia remains unclear. There is very little research about the hemodynamic variation induced by carotid tortuosity/kinking in the literature. The objective of this study was to research the blood pressure changes induced by carotid tortuosity/kinking. Methods. We first created a geometric model of carotid tortuosity/kinking. Based on hemodynamic boundary conditions, the hemodynamics of carotid tortuosity and kinking were studied via a finite element simulation. Then, an in vitro system was built to validate the numerical simulation results. The mean arterial pressure changes before and after carotid kinking were measured using pressure sensors in 12 patients with carotid kinking. Results. Numerical simulation revealed that the pressure drops increased with increases in the kinking angles. Clinical tests and in vitro experiments confirmed the numerical simulation results. Conclusions. Carotid kinking leads to blood pressure reduction. In certain conditions, kinking may affect the cerebral blood supply and be associated with cerebral ischemia.


Assuntos
Pressão Sanguínea , Artéria Carótida Interna/fisiopatologia , Simulação por Computador , Modelos Cardiovasculares , Adulto , Idoso , Doença das Coronárias/fisiopatologia , Diabetes Mellitus/fisiopatologia , Humanos , Hiperlipidemias/fisiopatologia , Hipertensão/fisiopatologia , Pessoa de Meia-Idade
9.
Zhonghua Wai Ke Za Zhi ; 54(5): 363-6, 2016 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-27143206

RESUMO

OBJECTIVE: To explore the feasibility, safety and efficacy of endovascular reconstructive treatment by multiple overlapping stents with or without coils. METHODS: Totally 17 patients of vertebrobasilar fusiform aneurysms treated by multiple overlapping stents with or without coils between September 2011 and September 2015 in Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. There were 15 male and 2 female patients with mean age of (47±13) years. Clinical manifestations included subarachnoid hemorrhage in 5 patients, cerebral ischemia or infarction in the posterior circulation in 5 patients, mass effect accompanied with brainstem infarction in 1 patients, headache or dizziness in 4, and incidental findings in 2 patients. Aneurysm located in intracranial vertebral artery in 11 patients, vertebrobasilar junction in 2 patients, and basilar trunk in 4 patients. Mean aneurysmal size was 18.5 mm×8.0 mm(length×width). RESULTS: Sole stenting with overlapping stents was performed in 8 patients, and overlapping stents with coils was applied in 9 patients. Post-procedural hemorrhage occurred in a patient with a giant basilar trunk fusiform aneurysm and led to death. The 16 surviving patients were clinically followed up for a mean of 21.1 months. One patient had a modified Rankin score of 4, and the other patients had a good recovery. Among 15 patients with a mean angiographic follow-up of 8.6 months, 9 patients had their aneurysms further thrombosed, 3 patients were stable, and 3 patients with a recurred aneurysm. Final complete occlusion was achieved in 7 patients. CONCLUSION: Reconstructive treatment by overlapping stents with or without coils is feasible and relative safe in vertebrobasilar fusiform aneurysms.


Assuntos
Procedimentos Endovasculares , Aneurisma Intracraniano/cirurgia , Stents , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento , Artéria Vertebral/patologia
10.
Bioorg Med Chem Lett ; 25(22): 5052-7, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26490095

RESUMO

Three series of 1,3-diaryl pyrazole derivatives bearing aminoguanidine or furan-2-carbohydrazide moieties have been synthesized, characterized and evaluated for antibacterial and anti-inflammatory activities. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains with minimum inhibitory concentration values in the range of 1-64 µg/mL. Compounds 6g, 6l and 7l presented the most potent inhibitory activity against Gram-positive bacteria (e.g. Staphylococcus aureus 4220), Gram-negative bacteria (e.g. Escherichia coli 1924) and the fungus, Candida albicans 7535, with minimum inhibitory concentration values of 1 or 2 µg/mL. Compared with previous studies, these compounds exhibited a broad spectrum of inhibitory activity. Furthermore, compound 7l showed the greatest anti-inflammatory activity (93.59% inhibition, 30 min after intraperitoneal administration), which was more potent than the reference drugs ibuprofen and indomethacin.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Furanos/farmacologia , Pirazóis/farmacologia , Animais , Antibacterianos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Antifúngicos/síntese química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Furanos/síntese química , Furanos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Cocos Gram-Positivos/efeitos dos fármacos , Ibuprofeno/farmacologia , Indometacina/farmacologia , Camundongos , Pirazóis/síntese química
11.
Zhonghua Wai Ke Za Zhi ; 53(7): 538-42, 2015 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-26359079

RESUMO

OBJECTIVE: To evaluate the short-term outcome of single stenting technique for unruptured, wide-necked, tiny aneurysms of the anterior circulation. METHODS: Eleven unruptured, wide-necked, tiny aneurysms of the anterior circulation were treated by a single stent deployed in the parent artery between January 2008 and July 2013 in Department of Neurosurgery in Beijing Hospital. The maximum diameter of the aneurysms ranged from 2.0 to 3.0 mm, mean (2.4 ± 0.4) mm, and the dome-to-neck ratios were all ≤ 1.2. The locations were clinoid segment of internal carotid artery (n=2), posterior communicating artery origin (n=4), anterior choroidal artery origin (n=2) and middle cerebral artery bifurcation (n=3). All internal carotid aneurysms were located in the medial and/or ventral wall of the internal carotid artery. The rate of aneurysm obliteration and rupture during follow-up was obtained by repeat angiography and clinic or telephone interview respectively. RESULTS: Sole stent placement in the parent artery was intentionally performed for nine aneurysms, while attempt of coiling after stent deployment for the other two aneurysms failed due to unsuccessful microcatherization. Ten stents were successfully deployed, of which one was used to treat two tandem lesions simultaneously. Only one aneurysm became smaller immediately postprocedure. No perioperative complications occurred. Angiographic follow-up after a mean period of (13 ± 6) months (range 8-24 months) revealed that 8 aneurysms did no change in size, 2 became smaller and only one was totally occluded. Asymptomatic in-stent stenosis of the parent artery was found in all 3 shrinking or occluded aneurysms. No aneurysm rupture was observed in the clinical follow-up. CONCLUSION: For those unruptured, wide-necked, tiny aneurysms arising at branching sites in the anterior circulation, single stenting technique seems to be a safe alternative treatment, while the short-term rate of aneurysm occlusion is low.


Assuntos
Procedimentos Cirúrgicos Cardiovasculares/métodos , Doenças das Artérias Carótidas/cirurgia , Aneurisma Intracraniano/cirurgia , Stents , Aneurisma Roto , Pequim , Artéria Carótida Interna/patologia , Angiografia Cerebral , Constrição Patológica , Humanos , Resultado do Tratamento
12.
Bioorg Med Chem Lett ; 25(15): 3052-6, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26048807

RESUMO

Three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a-k, 6a-i, and 7a-i) have been synthesized, characterized and evaluated for their antibacterial activity. Some of these displayed potent antibacterial activity against several Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 4-64 µg/mL and minimum bactericidal concentration (MBC) values in the range of 8-256 µg/mL. Compared with previously reported rhodanine derivatives, these compounds exhibited a broad spectrum of antibacterial activity by means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably, compound 5f exhibited good antibacterial activity against Staphylococcus aureus RN 4220, S. aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 or 16 µg/ml. All of the compounds synthesized in the current Letter were characterized by (1)H NMR, (13)C NMR, infrared and mass spectroscopy.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Rodanina/análogos & derivados , Rodanina/farmacologia , Triazóis/química , Triazóis/farmacologia , Anti-Infecciosos/síntese química , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Rodanina/síntese química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Tionas/síntese química , Tionas/química , Tionas/farmacologia , Triazóis/síntese química
13.
Interv Neuroradiol ; 20(6): 755-60, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25496687

RESUMO

Endovascular stenting with a balloon expandable device is currently the preferred treatment modality for symptomatic proximal vertebral artery stenosis, but high rates of in-stent restenosis remain a major problem, for which stent fracture might be a contributing factor. Limited reports showed that placement of self-expanding stents in the proximal vertebral artery might reduce restenosis; no stent fracture has been reported to date. We describe here a new case of fracture and occlusion of a self-expanding stent after endovascular treatment of symptomatic vertebral artery ostium stenosis.


Assuntos
Stents , Insuficiência Vertebrobasilar/terapia , Idoso , Angioplastia com Balão , Oclusão com Balão , Angiografia Cerebral , Procedimentos Endovasculares , Falha de Equipamento , Oclusão de Enxerto Vascular , Humanos , Masculino , Inibidores da Agregação de Plaquetas/uso terapêutico , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Artéria Vertebral/cirurgia , Insuficiência Vertebrobasilar/diagnóstico por imagem
14.
Bioorg Med Chem Lett ; 24(7): 1737-41, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24636107

RESUMO

Four series of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted piperazine moieties were synthesized and evaluated for their positive inotropic activity by measuring the left atrium stroke volume in isolated rabbit-heart preparations. Several compounds were developed and showed favorable activities compared to the standard drug milrinone, with (4-([1,2,4]triazolo[3,4-a]phthalazin-6-yl)piperazin-1-yl)(p-tolyl)methanone (5g) being identified as the most potent with an increased stroke volume of 19.15±0.22% (milrinone: 2.46±0.07%) at a concentration of 3×10(-5) M. A preliminary study of mechanism of action revealed that 5g displayed its positive inotropic effect may be related to the PDE-cAMP-PKA signaling pathway. Compounds exhibiting inotropic effects were also evaluated in terms of the chronotropic effects.


Assuntos
Ftalazinas/farmacologia , Piperazinas/química , Volume Sistólico/efeitos dos fármacos , Triazóis/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Ftalazinas/síntese química , Ftalazinas/química , Piperazina , Coelhos , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
15.
Eur J Med Chem ; 74: 405-10, 2014 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-24487189

RESUMO

Two novel series of 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)-2-thioxothiazolidin-4-one derivatives were designed and synthesized, and their anti-bacterial activities evaluated. These compounds showed broad-spectrum inhibitory activities against both Gram-positive and Gram-negative bacteria with minimum inhibitory concentration (MIC) values in the range of 1-64 µg/mL. The activity of compound 6c was the more potent with MIC values of 1 µg/mL against the MRSA (3167 and 3506) strains than those of gatifloxacin, oxacillin, and norfloxacin. Compared to the previously reported rhodanine derivatives, 2-thioxothiazolidin-4-one derivatives exhibited an inhibition against Gram-negative strains due to the introduction of a 1,3,4-oxadiazole moiety, among which compounds 3 showed moderate activities against the Gram-negative bacteria (Escherichiacoli 1924) with MIC values of 16 µg/mL.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Tiazolidinas/síntese química , Tiazolidinas/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria Infravermelho
16.
Interv Neuroradiol ; 20(1): 13-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24556295

RESUMO

Agenesis of carotid or vertebrobasilar arteries with rete formation is rare. The anterior spinal artery or posterior spinal arteries supplying the posterior circulation with steno-occlusion or agenesis of bilateral vertebral arteries is also uncommon. Here, we describe a very rare case of concomitant segmental agenesis of bilateral carotid and vertebral arteries with collateral compensations from the prominent anterior spinal artery and posterior spinal arteries, as well as some transdural arterial networks which were considered a rete mirabile. We discuss its embryological and anatomic significance.


Assuntos
Artérias Carótidas/anormalidades , Artérias Carótidas/diagnóstico por imagem , Microvasos/anormalidades , Microvasos/diagnóstico por imagem , Medula Espinal/irrigação sanguínea , Artéria Vertebral/anormalidades , Artéria Vertebral/diagnóstico por imagem , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Radiografia , Medula Espinal/diagnóstico por imagem
17.
J Neurointerv Surg ; 6(5): 384-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23761480

RESUMO

OBJECTIVE: To investigate the working memory of patients with cervicocerebral artery stenosis and its change after stenting. METHODS: 35 patients with cervicocerebral artery stenosis (≥50% with related symptoms of cerebral ischemia, or ≥70% with or without related symptoms of cerebral ischemia) underwent endovascular stenting. Working memory of all 35 patients before and within 3 weeks of stenting was evaluated by memory quotient (MQ) scores. Change in regional cerebral blood flow (rCBF) was assessed by single photon emission CT (SPECT) for 13 of the patients. MQ scores were compared according to location and degree of stenosis for all patients, as well as changes in rCBF for the 13 patients. RESULTS: Mean MQ scores were significantly lower than normal for patients with carotid artery stenosis alone and for patients with carotid stenosis in addition to vertebrobasilar and/or subclavical stenosis, but not for patients with vertebrobasilar and/or subclavical stenosis. MQ scores were significantly increased after stenting for all patients, especially those with carotid stenosis. There was no significant difference between patients with moderate stenosis and those with severe (>70%) stenosis in MQ increments pre- and post-stenting (p=0.085). Nine of the 13 patients who received SPECT showed an improvement in rCBF after stenting, and their MQ increments were significantly higher than those without an improvement in rCBF (p=0.020). CONCLUSIONS: Working memory impairment can be observed in patients with cervicocerebral artery stenosis, especially those with carotid stenosis. Endovascular stenting of stenosis might improve the impairment by alleviating cerebral perfusion deficit.


Assuntos
Isquemia Encefálica/cirurgia , Estenose das Carótidas/cirurgia , Revascularização Cerebral/métodos , Transtornos da Memória/cirurgia , Memória de Curto Prazo , Stents , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etiologia , Estenose das Carótidas/complicações , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
18.
Zhonghua Wai Ke Za Zhi ; 50(1): 70-3, 2012 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-22490296

RESUMO

OBJECTIVES: To study the relationship between serum levels of some inflammatory markers and stability of carotid plaques in the patients with carotid plaques and evaluate the ability of each serum marker in identifying vulnerable carotid plaques. METHODS: The study included 65 consecutive patients with carotid plaques confirmed by imaging examinations from March 2008 to March 2010. All the patients were classified as stable plaques group (n = 21) and unstable plaques group (n = 44) according to the characteristic findings of the plaques in MRI such as the thickness of fibrous cap, the existence of large lipid core and the intra-plaque hemorrhage. The patients of unstable plaques group were further classified as unruptured plaques group (n = 29) and rupture plaques group (n = 15) according to the integrity of fibrous cap. Serum levels of soluble cluster of differentiation 40 ligand (sCD40L), matrix metalloproteinase 9 (MMP-9) and pregnancy-associated plasma protein A (PAPP-A) were determined by ELISA. RESULTS: Serum levels of sCD40L and MMP-9 in patients of unstable plaques group, unruptured plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group (SCD40L: χ(2) = 6.45, 12.04 and 16.23, P < 0.01; MMP-9; F = 2.55, 5.10 and 4.69, P < 0.05). Serum levels of PAPP-A in patients of unstable plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group (χ(2) = 11.71 and 13.55, P < 0.05). Serum levels of PAPP-A in patients of rupture plaques group were significantly enhanced compared to individuals of unruptured plaques group (χ(2) = 13.19, P = 0.000). sCD40L ≥ 673.22 ng/L (OR = 22.47, 95%CI: 2.11 - 239.81, P = 0.010), MMP-9 ≥ 84.09 µg/L (OR = 10.01, 95%CI: 1.74 - 57.78, P = 0.010) and PAPP-A ≥ 0.101 µg/L (OR = 14.29, 95%CI: 2.69 - 75.90, P = 0.002) were all significantly correlated with the vulnerability of carotid plaques. CONCLUSIONS: There appear to be a relationship between the serum levels of sCD40L, MMP-9 and PAPP-A and the stability of carotid plaques in patients with carotid plaques. High serum levels of the above-mentioned markers may indicate that the plaques were vulnerable or ruptured.


Assuntos
Ligante de CD40/sangue , Estenose das Carótidas/sangue , Metaloproteinase 9 da Matriz/sangue , Proteína Plasmática A Associada à Gravidez/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Eur J Radiol ; 81(6): 1276-81, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21435809

RESUMO

PURPOSE: Tiny intracranial aneurysms pose a significant therapeutic challenge for interventional neuroradiologists. The authors report their preliminary results of endovascular treatment of these aneurysms. METHODS: Between January 2002 and December 2009, 52 tiny intracranial aneurysms (defined as ≤ 3 mm in maximum diameter) in 46 patients (22 men; mean age, 57.9 years) were treated by endosaccular coil embolisation or sole stent deployment in the parent artery. Of 52 aneurysms, 29 had ruptured and 23 remained unruptured. The initial angiographic results, procedural complications, and clinical outcomes were assessed at discharge. Imaging follow-up was performed with cerebral angiography. RESULTS: One aneurysm coiling procedure failed because of unsuccessful micro-catheterization. Forty-three aneurysms were successfully coil embolized, of which complete occlusion was obtained in 14, subtotal occlusion in 18 and incomplete occlusion in 11. The other 8 aneurysms were treated by sole stent deployment in the parent artery. Procedural complications (2 intraprocedural ruptures and 3 thromboembolic events) occurred in 5 (9.6%) of 52 aneurysms, resulting in permanent morbidity in only 1 (2.2%, 1/46) patient. No rebleeding occurred during clinical follow-up (mean duration, 46.7 months). Of the 16 coiled aneurysms that receiving repetitive angiography, 6 initially completely and 3 subtotally occluded aneurysms remained unchanged, 4 initially subtotally and 3 incompletely occluded aneurysms progressed to total occlusion. Five sole stent deployed aneurysms received angiographic follow-up (mean duration, 10.0 months), of which 3 remained unchanged, 1 became smaller and 1 progressed to total occlusion. CONCLUSION: Endovascular treatment of tiny intracranial aneurysms is technical feasible and relatively safe. Coil embolisation seems to be effective in preventing early recanalisation, whereas sole stenting technique needs further investigation to determine its effectiveness.


Assuntos
Aneurisma Roto/terapia , Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/patologia , Cateterismo , Angiografia Cerebral , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Stents/efeitos adversos , Resultado do Tratamento
20.
Zhonghua Wai Ke Za Zhi ; 49(2): 105-8, 2011 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-21426822

RESUMO

OBJECTIVE: To study the necessity, feasibility, security of carotid angioplasty and stenting (CAS) for symptomatic carotid stenosis combined with kinking. METHODS: Twelve patients with symptomatic carotid stenosis and kinking demonstrated by digital subtraction angiography (DSA) received CAS from December 2003 to December 2009. There were 9 male and 3 female patients, age ranged from 59 to 77 years (mean 69.3 years). All the patients' clinical, imaging, intervention and follow up data were collected and analyzed. RESULTS: All CAS procedures were successfully performed with 14 self-expandable stents placed. The mean degree of stenosis was reduced from 85.6% before stenting to 11.2% after stenting, the angle of kinking, according to Metz' category, were improved from less than 90° to more than 120° in each case. No perioperative procedure related stroke and transient ischemic attack (TIA) occurred. The clinical symptoms and signs of cerebral ischemia were improved or disappeared for all patients. During follow-up of these 12 patients for 6 to 72 months, one patient experienced ipsilateral carotid territory TIA and another patient experienced contralateral carotid territory TIA. DSA follow up of 5 patients demonstrated 1 case with in-stent restenosis and arterial kinking remote to the stent of internal carotid artery. CAS were performed again and CT angiography follow up demonstrated no kinking and restenosis 2 years after the intervention. Duplex scan of the other 7 patients demonstrated neither kinking nor restenosis. CONCLUSIONS: CAS seems to be feasible and safe for the patients with symptomatic kinking and stenosis, and maybe helpful to lower the risk of cerebral ischemia, but further study is needed.


Assuntos
Angioplastia com Balão/métodos , Estenose das Carótidas/cirurgia , Idoso , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Stents , Resultado do Tratamento
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