RESUMEN
Consolidating a microscopic understanding of magnetic properties is crucial for a rational design of magnetic materials with tailored characteristics. The interplay of 3d and 4f magnetism in rare-earth transition metal antimonides is an ideal platform to search for such complex behavior. Here the synthesis, crystal growth, structure, and complex magnetic properties are reported of the new compound Pr3 Fe3 Sb7 as studied by magnetization and electrical transport measurements in static and pulsed magnetic fields up to 56 T, powder neutron diffraction, and Mößbauer spectroscopy. On cooling without external magnetic field, Pr3 Fe3 Sb7 shows spontaneous magnetization, indicating a symmetry breaking without a compensating domain structure. The Fe substructure exhibits noncollinear ferromagnetic order below the Curie temperature TC ≈ 380 K. Two spin orientations exist, which approximately align along the Fe-Fe bond directions, one parallel to the ab plane and a second one with the moments canting away from the c axis. The Pr substructure orders below 40 K, leading to a spin-reorientation transition (SRT) of the iron substructure. In low fields, the Fe and Pr magnetic moments order antiparallel to each other, which gives rise to a magnetization antiparallel to the external field. At 1.4 K, the magnetization approaches saturation above 40 T. The compound exhibits metallic resistivity along the c axis, with a small anomaly at the SRT.
RESUMEN
A man in his 40s with Brugada syndrome underwent catheter ablation for ventricular fibrillation. When we performed epicardial mapping again to check for residual ablation sites after ablation, a remarkable reproducible fragmented potential was observed at the anterior aspect of the right ventricle using an Advisor HD Grid (Abbott), which had not been detected during the initial mapping before ablation, and which was invisible to the ablation catheter. Fluoroscopic imaging demonstrated a shiny area anterior to the heart, suggesting trapped air, presumed to have arisen when the sheath was inserted into the pericardial space. The air trapped between the heart and pericardium prevented the HD grid from contacting the epicardium, resulting in the recording of a fragmented potential. The trapped air was removed manually via the sheath, and the potential vanished. When fragmented potentials are observed at the anterior right ventricle (RV) in the epicardium, air trapping should be ruled out by fluoroscopy.
Asunto(s)
Síndrome de Brugada , Ablación por Catéter , Taquicardia Ventricular , Síndrome de Brugada/complicaciones , Ablación por Catéter/métodos , Electrocardiografía/métodos , Técnicas Electrofisiológicas Cardíacas/métodos , Mapeo Epicárdico/métodos , Humanos , Masculino , Pericardio/cirugía , Fibrilación VentricularRESUMEN
We report a 49-year-old male with castration-resistant prostate cancer (CRPC) with oligometastasis diagnosed by 11C-choline positron emission tomography-computed tomography (PET/CT) and treated with target radiotherapy. In the diagnosis of CRPC (serum prostate-specific antigen [PSA] level of 6.53 ng/mL after maximum androgen blockade (MAB) therapy, high-dose brachytherapy, and external beam radiotherapy), 11C-choline PET/CT detected one tiny obturator lymph node metastasis which fluorodeoxyglucose PET/CT could not detect. He underwent intensity-modulated radiation therapy and MAB was restarted. The PSA value decreased and reached nadir (0.091 ng/mL) after 6 months. The time to PSA progression was 10 months. The choline PET/CT finding and the corresponding local treatment could play an important role in the management sequence of oligoprogressive CRPC.
RESUMEN
OBJECTIVES: To compare the optimal administration period of antimicrobial prophylaxis in patients undergoing transurethral enucleation of the prostate for benign prostatic hyperplasia. METHODS: We carried out a randomized controlled trial to compare the differences in incidence of perioperative genitourinary tract infection between single and multiple (3 days) administrations of cefazolin for transurethral enucleation of the prostate in benign prostatic hyperplasia patients without pyuria or bacteriuria between January 2015 and December 2018. RESULTS: This multicenter randomized controlled trial included 203 patients who underwent a transurethral enucleation of the prostate procedure. All received antimicrobial prophylaxis, and were randomized into those who received single-dose (n = 101) or multiple-dose (n = 102) therapy. The rate of genitourinary tract infection after transurethral enucleation of the prostate for all patients was 1.5%, whereas that in the single-dose group was 1.0% and in the multiple-dose group was 2.0%, which were not significantly different (P = 1.00). CONCLUSIONS: A single dose of antimicrobial prophylaxis as a prophylactic antibacterial drug is sufficient for patients undergoing transurethral enucleation of the prostate who do not have presurgical pyuria or bacteriuria.
Asunto(s)
Terapia por Láser , Hiperplasia Prostática , Resección Transuretral de la Próstata , Infecciones Urinarias , Cefazolina/uso terapéutico , Humanos , Japón/epidemiología , Masculino , Estudios Prospectivos , Próstata/cirugía , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/efectos adversos , Resultado del Tratamiento , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Infecciones Urinarias/prevención & controlRESUMEN
Selenium is an essential trace element, and its deficiency can cause cardiomyopathy, arrhythmias and increased susceptibility to infection. Such clinical symptoms are considered primarily attributed to decreased expression of some of the 25 selenocysteine-containing selenoproteins in humans. Conversely, a selenium-excessive diet can cause acute poisoning and chronic symptoms with unknown mechanisms. To reveal the impact of selenium deficiency and excess on selenoprotein expression in vivo, mice (that possess 24 selenoproteins) were fed with selenium-deficient or selenomethionine-excessive diets for up to 4 weeks, and the expression levels of nine representative selenoproteins [glutathione peroxidase (Gpx) 1/2/3/4, thioredoxin reductase 1/2, deiodinase 1, and selenoprotein P/S] were measured in 10 organs (brain, heart, liver, lung, kidney, pancreas, spleen, testis, skeletal muscle and thymus). We observed a time-dependent decrease in the selenium content of most organs (except testis) of selenium-deficient mice but not in the expression levels of the nine selenoproteins, with the exceptions of Gpx1/2 in the heart/liver/kidney/pancreas/spleen and Gpx3 in the pancreas/spleen. Serum lipid peroxidation levels were up-regulated in response to Se deficiency because of the decreased expression/activity of Gpx3, a plasma-type Gpx. In contrast, a time-dependent increase was observed in the selenium content of all organs but not the expression levels of the nine selenoproteins in most organs of selenomethionine-excessive mice; however, markedly elevated protein-bound selenium levels were observed in the liver/kidney. These results suggest that the systemic response to selenium deficiency and selenomethionine excess involves the down-regulation of some selenoproteins such as Gpx1/Gpx3 and up-regulation of selenium-containing proteins (not selenoproteins), respectively.
Asunto(s)
Selenio/deficiencia , Selenio/metabolismo , Selenometionina/administración & dosificación , Selenoproteínas/metabolismo , Animales , Dieta , Glutatión Peroxidasa/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Selenio/farmacocinética , Selenoproteínas/genética , Distribución Tisular , Glutatión Peroxidasa GPX1RESUMEN
OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.
Asunto(s)
Extractos Vegetales/administración & dosificación , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Prostatitis/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/efectos adversos , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Próstata/patología , Neoplasias de la Próstata/patología , Curva ROC , Secale , Procedimientos InnecesariosRESUMEN
Choline is a new PET tracer, which uptake may occur via a choline-speciï¬c transporter protein and be accelerated during the proliferation of tumor cells. We report a 61-year-old woman with a metastatic pancreatic tumor from renal cell carcinoma, measuring 35×40 mm. PET scans demonstrated accumulation of 11C-choline in the metastatic pancreatic tumor, but no accumulation of 18F-FDG. Choline PET/CT may play a useful and complementary imaging modality, especially when FDG-PET/CT does not show expected findings or when the evaluation of tumor viability is needed, in patients with renal cell carcinoma.
Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Colina/química , Fluorodesoxiglucosa F18/análisis , Neoplasias Renales/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carcinoma de Células Renales/complicaciones , Femenino , Humanos , Neoplasias Renales/complicaciones , Persona de Mediana EdadRESUMEN
Elemental concentrations in hair and dried serum have been evaluated by X-ray fluorescence analysis using relative concentration independent of specimen thickness. Dried serum samples from 5 male and 5 female subjects given two-week Ca supplementation showed the same concentration for Ca, and for each of the other elements Cl, K, S and P under renal control by parathyroid hormone (PTH). Hair concentrations of these elements have been evaluated for 50 randomly-selected females aged between 30 and 80. It was found that each element has two distinct levels in hair. The content of an element in growing hair must be equal to the inflow of that element into the hair-making cells from serum. Using this principle, the two levels can be attributed to the gating and closing of the ion channels in cell membranes and given as functions of the dried serum standard concentrations. Especially, the difference between [Ca] and [Sr] in hair shows whether Ca channels are gating or closing. The lower level of hair [Ca]
Asunto(s)
Calcio/análisis , Cabello/química , Suero/química , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Proteínas Sanguíneas , Calcio/administración & dosificación , Calcio/deficiencia , Canales de Calcio , Femenino , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Espectrometría por Rayos X , Estroncio , SincrotronesRESUMEN
OBJECTIVES: The increasing prevalence of resistant bacteria such as fluoroquinolone-resistant or extended-spectrum ß-lactamase-producing strains in pathogens causing acute uncomplicated cystitis has been of concern in Japan. Faropenem sodium is a penem antimicrobial that demonstrates a wide antimicrobial spectrum against both aerobic and anaerobic bacteria. It is stable against a number of ß-lactamases. METHODS: We compared 3 and 7 day administration regimens of faropenem in a multicentre, randomized, open-label, controlled study. RESULTS: In total, 200 female patients with cystitis were enrolled and randomized into 3 day (Nâ=â97) or 7 day (Nâ=â103) treatment groups. At the first visit, 161 bacterial strains were isolated from 154 participants, and Escherichia coli accounted for 73.9% (119/161) of bacterial strains. At 5-9 days after the completion of treatment, 73 and 81 patients from the 3 day and 7 day groups, respectively, were evaluated by intention-to-treat analysis; the microbiological efficacies were 58.9% eradication (43/73), 20.5% persistence (15/73) and 8.2% replaced (6/73), and 66.7% eradication (54/81), 6.2% persistence (5/81) and 7.4% replaced (6/81), respectively (Pâ=â0.048). The clinical efficacies were 76.7% (56/73) and 80.2% (65/81), respectively (Pâ=â0.695). Adverse events due to faropenem were reported in 9.5% of participants (19/200), and the most common adverse event was diarrhoea. CONCLUSIONS: The 7 day regimen showed a superior rate of microbiological response. E. coli strains were in general susceptible to faropenem, including fluoroquinolone- and cephalosporin-resistant strains.
Asunto(s)
Antibacterianos/uso terapéutico , Cistitis/tratamiento farmacológico , beta-Lactamas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Cistitis/microbiología , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven , beta-Lactamas/farmacologíaRESUMEN
A low n-3 to n-6 polyunsaturated fatty acid (PUFA) ratio is associated with cardiovascular events. However, the effects of this ratio on coronary atherosclerosis have not been fully examined, particularly in patients treated with different types of statins. This study compared the effects of n-3 to n-6 PUFA ratios on coronary atherosclerosis in patients treated with pitavastatin and pravastatin. Coronary atherosclerosis in nonculprit lesions in the percutaneous coronary intervention vessel was evaluated using virtual histology intravascular ultrasound in 101 patients at the time of percutaneous coronary intervention and 8 months after statin therapy. Pitavastatin and pravastatin were used to treat 51 and 50 patients, respectively. Changes in the docosahexaenoic acid (DHA)/arachidonic acid (AA) and eicosapentaenoic acid+DHA/AA ratios were not correlated with the percentage change in plaque volume in the pitavastatin group, whereas the percentage change in plaque volume and the changes in the DHA/AA ratio (r = -0.404, p = 0.004) and eicosapentaenoic acid+DHA/AA ratio (r = -0.350, p = 0.01) in the pravastatin group showed significant negative correlations. Multivariate regression analysis showed that age (ß = 0.306, p = 0.02), the presence of diabetes mellitus (ß = 0.250, p = 0.048), and changes in the DHA/AA ratio (ß = -0.423, p = 0.001) were significant predictors of the percentage change in plaque volume in patients treated with pravastatin. In conclusion, decreases in n-3 to n-6 PUFA ratios are associated with progression in coronary atherosclerosis during pravastatin therapy but not during pitavastatin therapy.
Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Intervención Coronaria Percutánea , Pravastatina/uso terapéutico , Quinolinas/uso terapéutico , Ultrasonografía Intervencional/métodos , Anciano , Aterosclerosis/sangre , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/terapia , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Pravastatina/administración & dosificación , Estudios Prospectivos , Quinolinas/administración & dosificación , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: A low n-3 to n-6 polyunsaturated fatty acids (PUFAs) ratio is reported to be associated with cardiovascular events. However, the effects of statins on this ratio have not been fully examined. METHODS: A total of 101 patients with coronary artery disease, who were not receiving lipid-lowering therapy were randomly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of pravastatin. Serum PUFA levels were measured at baseline and 8 months after treatment with statins. RESULTS: Pitavastatin was used to treat 51 patients and the remaining 50 patients were treated using pravastatin. A significant positive correlation was observed between the percent change in low-density lipoprotein cholesterol and that in dihomogamma-linolenic acid (r = .376, P = .007), arachidonic acid (AA; r = .316, P = .02), eicosapentaenoic acid (EPA; r = .408, P = .003), or docosahexaenoic acid (DHA; r = .270, P = .056) in the pitavastatin group. However, these correlations were not observed in the pravastatin group. The DHA/AA ratio decreased significantly in the pitavastatin group only (from 0.96 to 0.83, P = .0002) and the DHA/AA ratio was significantly lower in the pitavastatin group at 8 months (0.83 vs 0.96, P = .03). The EPA/AA ratio did not show significant changes in either group. CONCLUSIONS: Pitavastatin decreased the serum DHA/AA ratio, whereas pravastatin had no effect on this ratio. Neither pitavastatin nor pravastatin had an effect on the serum EPA/AA ratio in patients with coronary artery disease.
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LDL-Colesterol/efectos de los fármacos , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Anciano , Ácido Araquidónico/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Femenino , Humanos , Japón , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pravastatina/uso terapéutico , Estudios Prospectivos , Quinolinas/uso terapéutico , Ácido alfa-Linolénico/sangreRESUMEN
We examined the rate of relapse, as a variable index, in patients with urinary tract infection (UTI) who suffered from multiple relapses when using cranberry juice (UR65). A randomized, placebo-controlled, double-blind study was conducted from October 2007 to September 2009 in Japan. The subjects were outpatients aged 20 to 79 years who were randomly divided into two groups. One group received cranberry juice (group A) and the other a placebo beverage (group P). To keep the conditions blind, the color and taste of the beverages were adjusted. The subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of UTI. In the group of females aged 50 years or more, there was a significant difference in the rate of relapse of UTI between groups A and P (log-rank test; p = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55 (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study, cranberry juice prevented the recurrence of UTI in a limited female population with 24-week intake of the beverage.
Asunto(s)
Bebidas , Proantocianidinas/uso terapéutico , Prevención Secundaria , Infecciones Urinarias/prevención & control , Vaccinium macrocarpon , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Fitoterapia , Adulto JovenRESUMEN
A low ratio of n-3 to n-6 polyunsaturated fatty acids has been associated with cardiovascular events. However, the effects of this ratio on coronary atherosclerosis have not been fully examined. The purpose of the present study was to evaluate the correlations between the n-3 to n-6 polyunsaturated fatty acid ratio and coronary atherosclerosis. Coronary atherosclerosis in nonculprit lesions in the percutaneous coronary intervention vessel was evaluated using virtual histology intravascular ultrasound in 101 patients at the time of percutaneous coronary intervention and 8 months after statin therapy. Forty-six patients (46%) showed atheroma progression and the remaining 55 patients (54%) showed atheroma regression at 8-month follow-up. Significant negative correlations were observed between percentage change in plaque volume and change in the eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (r = -0.190, p = 0.05), docosahexaenoic acid (DHA)/AA ratio (r = -0.231, p = 0.02), and EPA+DHA/AA ratio (r = -0.240, p = 0.02). Furthermore, percentage change in the fibrous component volume was negatively and significantly correlated with change in the EPA/AA ratio (r = -0.206, p = 0.04) and EPA+DHA/AA ratio (r = -0.217, p = 0.03). Multivariate regression analysis showed that change in the EPA+DHA/AA ratio was a significant predictor of percentage change in plaque volume and fibrous component volume (ß = -0.221, p = 0.02, and ß = -0.200, p = 0.04, respectively). In conclusion, decreases in serum n-3 to n-6 polyunsaturated fatty acid ratios are associated with progression in coronary atherosclerosis evaluated using virtual histology intravascular ultrasound in statin-treated patients with coronary artery disease.
Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Anciano , Biomarcadores/sangre , Cromatografía de Gases , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Vasos Coronarios/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pravastatina/uso terapéutico , Estudios Prospectivos , Quinolinas/uso terapéutico , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
To assess the clinical efficacy of oral antibiotic administration for the treatment of lower urinary tract infection (UTI), 102 female patients were given gatifloxacin (200 mg once daily for 3 days). Five to nine days after treatment, drug safety and clinical efficacy were assessed by evaluation of urinalysis and symptoms. Further, the patients were asked to report by mail whether they had persistent or recurrent symptoms at 4-6 weeks after treatment. The overall clinical cure rate was 93.1% (95/102). Of 94 patients with susceptible pathogens and 8 with resistant pathogens, 89 (94.7%) and 6 (75.0%), respectively, were judged as clinically cured. Four to 6 weeks after treatment, 57 (55.9%) of the 102 patients reported their micturition status by mail, and 6 (10.5%) of them claimed that they had some symptoms. The outcomes of this study suggest that a therapeutic regimen such as administration of fluoroquinolones once daily for 3 days can be recommended for the treatment of uncomplicated cystitis.
Asunto(s)
Antiinfecciosos/administración & dosificación , Cistitis/tratamiento farmacológico , Fluoroquinolonas/administración & dosificación , Adulto , Antiinfecciosos/efectos adversos , Antiinfecciosos/uso terapéutico , Cistitis/microbiología , Esquema de Medicación , Femenino , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/uso terapéutico , Gatifloxacina , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Piuria , Resultado del TratamientoRESUMEN
A series of 4-(4-phenoxy)benzoylamino-4-methoxymethyloxymethyl butyric acid hydroxamates, which were derived from l-glutamic acid, were synthesized and evaluated as matrix metalloproteinase inhibitors. Most of the compounds listed in exhibited strong inhibitory activity against MMP-2 and MMP-9, as well as even stronger inhibitory activity against MMP-3, but showed relatively weak inhibition of MMP-1. Structure-activity relationships are discussed.
Asunto(s)
Benzamidas , Diseño de Fármacos , Ácidos Hidroxámicos , Inhibidores de la Metaloproteinasa de la Matriz , Inhibidores de Proteasas , Administración Oral , Animales , Benzamidas/síntesis química , Benzamidas/química , Benzamidas/farmacología , Evaluación Preclínica de Medicamentos , Activación Enzimática/efectos de los fármacos , Ácido Glutámico/química , Cobayas , Ácidos Hidroxámicos/síntesis química , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Masculino , Conformación Molecular , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/síntesis química , Inhibidores de Proteasas/química , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
A series of N-benzoyl 4-aminobutyric acid hydroxamate analogs were synthesized and evaluated as matrix metalloproteinase inhibitors. Synthetic work was focused on the chemical modification of the 4-aminobutyric acid part using easily available starting materials. As such, chemical modification was carried out using commercially available starting materials such as 4-aminobutyric acid, (+)- and (-)-malic acid, and D- and L-glutamic acid derivatives. Among the compounds tested, N-[4-(benzofuran-2-yl)benzoyl] 4-amino-4S-hydroxymethylbutyric acid hydroxamates derived from L-glutamic acid demonstrated more potent inhibitory activity against MMP-2 and MMP-9 compared with the corresponding 2S-hydroxy analogs or 3S-hydroxy analogs, respectively, which were derived from (-)-malic acid. Structure-activity relationship study is presented.