Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Arch Pharm (Weinheim) ; 350(11)2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28940630

RESUMEN

Alzheimer's disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC50 values of 0.64-51.09 µM. The preliminary structure-activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole and alkylsulfonyl chains. Molecular dynamics studies of compound 6d showed that the interaction with the peripheral binding site of AChE was similar to donepezil, which may explain its low IC50 (0.64 µM). Furthermore, the drug-likeness of 6d suggests that the compound may have appropriate oral absorption and brain penetration. Compound 6d also presented antiradical activity and was not cytotoxic to LL24 cells, suggesting that this compound might be considered safe. Our findings indicate that arylsulfonylhydrazones may be a promising scaffold for the design of new drug candidates for the treatment of AD.


Asunto(s)
Acetilcolinesterasa/efectos de los fármacos , Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/farmacología , Hidrazonas/farmacología , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/enzimología , Sitios de Unión , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Donepezilo , Diseño de Fármacos , Humanos , Hidrazonas/síntesis química , Hidrazonas/química , Indanos/farmacología , Concentración 50 Inhibidora , Modelos Moleculares , Piperidinas/farmacología , Relación Estructura-Actividad
2.
Bioorg Med Chem ; 24(19): 4600-4610, 2016 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-27561984

RESUMEN

A series of novel chelerythrine analogues was designed and synthesized. Antitumor activity was evaluated against A549, NCI-H1299, NCI-H292, and NCI-H460 non-small-cell lung cancer (NSCLC) cell lines in vitro. The selectivity of the most active analogues and chelerythrine was also evaluated, and we compared their cytotoxicity in NSCLC cells and non-tumorigenic cell lines, including human umbilical vein endothelial cells (HUVECs) and LL24 human lung fibroblasts. In silico studies were performed to establish structure-activity relationships between chelerythrine and the analogues. The results showed that analogue compound 3f induced significant dose-dependent G0/G1 cell cycle arrest in A549 and NCI-H1299 cells. Theoretical studies indicated that the molecular arrangement and electron characteristics of compound 3f were closely related to the profile of chelerythrine, supporting its activity. The present study presents a new and simplified chelerythrinoid scaffold with enhanced selectivity against NSCLC tumor cells for further optimization.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Benzofenantridinas/química , Benzofenantridinas/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Pulmón/efectos de los fármacos , Pulmón/patología , Neoplasias Pulmonares/patología , Modelos Moleculares , Relación Estructura-Actividad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA