RESUMEN
1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal structure data shows the inhibitor 1 bound in the enzyme active site of E. coli FabI.
Asunto(s)
Antibacterianos/farmacología , Imidazoles/farmacología , Oxidorreductasas/antagonistas & inhibidores , Antibacterianos/síntesis química , Antibacterianos/química , Enoil-ACP Reductasa (NADH) , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli , Acido Graso Sintasa Tipo II , Imidazoles/síntesis química , Imidazoles/química , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacosRESUMEN
INTRODUCTION: Motor neuron diseases are always lethal. Other curable causes of neurologic disorders have to be sought. We report an example. EXEGESIS: A 72-year-old man presented a distal weakness and atrophy of the upper extremities. Electromyography showed thenar and hypothenar denervation, without fasciculation. Hypercalcemia led to the discovery of a primary hyperparathyroidism. Five months after parathyroid surgery, there was no worsening. CONCLUSION: Von Recklinghausen and Vical were the first to describe neuromuscular involvement in primary hyperparathyroidism. Faced with symptoms mimicking motor neuron diseases, calcium and phosphorus levels have to be measured because hyperparathyroidism can be cured and neurologic disorders disappear after surgery.
Asunto(s)
Esclerosis Amiotrófica Lateral/diagnóstico , Hiperparatiroidismo/diagnóstico , Adenoma/diagnóstico , Adenoma/cirugía , Anciano , Calcio/sangre , Diagnóstico Diferencial , Electromiografía , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiología , Hiperparatiroidismo/sangre , Hiperparatiroidismo/etiología , Masculino , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/cirugía , Paratiroidectomía , Fósforo/sangreRESUMEN
The activity of a novel series of peptidomimetic hematoregulatory compounds, designed based on a pharmacophore model inferred from the structure activity relationships of a peptide SK&F 107647 (1), is reported. These compounds induce a hematopoietic synergistic factor (HSF) which in turn modulates host defense. The compounds may represent novel therapeutic agents in the area of hematoregulation.
Asunto(s)
Fármacos Cardiovasculares/síntesis química , Quimiocinas CXC , Péptidos y Proteínas de Señalización Intercelular , Oligopéptidos/farmacología , Aminoácidos/química , Animales , Candidiasis/tratamiento farmacológico , Fármacos Cardiovasculares/farmacología , Fármacos Cardiovasculares/uso terapéutico , Línea Celular , Quimiocina CXCL1 , Factores Quimiotácticos/metabolismo , Diseño de Fármacos , Factor Estimulante de Colonias de Granulocitos/biosíntesis , Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Sustancias de Crecimiento/metabolismo , Factor Estimulante de Colonias de Macrófagos/biosíntesis , Ratones , Oligopéptidos/química , Receptores de Droga/química , Receptores de Droga/efectos de los fármacosAsunto(s)
Benzazepinas/farmacología , Piridinas/farmacología , Receptores de Vitronectina/antagonistas & inhibidores , Animales , Benzazepinas/síntesis química , Benzazepinas/farmacocinética , Disponibilidad Biológica , Resorción Ósea/prevención & control , Adhesión Celular/efectos de los fármacos , Línea Celular , Semivida , Humanos , Imitación Molecular , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Piridinas/síntesis química , Piridinas/farmacocinética , Ratas , Estereoisomerismo , Distribución TisularRESUMEN
Hematopoiesis is a lifelong cell renewal process regulated by a family of lineage specific hematopoietic growth factors. Several hematopoietic growth factors such as G-CSF, GM-CSF, and M-CSF have been clinically evaluated for enhancement of host defense in normal and immunocompromised patients and for the treatment of infectious diseases. This paper reports the structure-activity relationships of low molecular weight hematoregulatory peptides based on a nonapeptide (1, SK&F 107647). Like the macromolecular growth factors, these peptides modulate host defense. A molecular target for this class of compounds has not yet been identified. However, the structure-activity relationships established by this study implicate a very specific molecular recognition event that is pivotal for the biological activities of 1 and its analogues.