RESUMEN
The Giardia genome project database provides an online resource for Giardia lamblia (WB strain, clone C6) genome sequence information. The database includes edited single-pass reads, the results of BLASTX searches, and details of progress towards sequencing the entire 12 million-bp Giardia genome. Pre-sorted BLASTX results can be retrieved based on keyword searches and BLAST searches of the high throughput Giardia data can be initiated from the web site or through NCBI. Descriptions of the genomic DNA libraries, project protocols and summary statistics are also available. Although the Giardia genome project is ongoing, new sequences are made available on a bi-monthly basis to ensure that researchers have access to information that may assist them in the search for genes and their biological function. The current URL of the Giardia genome project database is www.mbl.edu/Giardia.
Asunto(s)
Bases de Datos Factuales , Genoma de Protozoos , Giardia/genética , AnimalesRESUMEN
A series of novel N-(4-pyridinyl)-1H-indol-1-amines and other heteroaryl analogs was synthesized and evaluated in tests to determine potential utility for the treatment of Alzheimer's disease. From these compounds, N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine, 4c) was selected for clinical development based on in-depth biological evaluation. In addition to cholinomimetic properties based initially on in vitro inhibition of [3H]quinuclidinyl benzilate binding, in vivo reversal of scopolamine-induced behavioral deficits, and subsequently on other results, 4c also displayed enhancement of adrenergic mechanisms as evidenced in vitro by inhibition of [3H] clonidine binding and synaptosomal biogenic amine uptake, and in vivo by reversal of tetrabenazine-induced ptosis. The synthesis, structure-activity relationships for this series, and the biological profile of 4c are reported.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Indoles/síntesis química , Indoles/farmacología , Parasimpatolíticos/síntesis química , Parasimpatolíticos/farmacología , Piridinas/síntesis química , Piridinas/farmacología , Animales , Aminas Biogénicas/antagonistas & inhibidores , Aminas Biogénicas/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Técnicas In Vitro , Indoles/uso terapéutico , Espectroscopía de Resonancia Magnética , Parasimpatolíticos/uso terapéutico , Piridinas/uso terapéutico , Ratas , Relación Estructura-ActividadRESUMEN
A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Compounds displaying significant activity were more broadly evaluated, which revealed the presence of a desirable adrenergic component of activity. The synthesis and structure-activity relationships for this series is presented, along with the biological profiles of selected compounds.