RESUMEN
Many drugs induce severe side-effects caused by their lack of selectivity. One way to overcome this problem is to design a specific system which releases a free drug in a controlled manner. Herein we describe a new way to liberate a drug from a prodrug using the Staudinger ligation as the trigger.
Asunto(s)
Profármacos/química , Aminas/química , Doxorrubicina/química , Estructura MolecularRESUMEN
As HIV-associated dementia prevalence has risen with the lifespan of HIV-infected individuals, there is an important need for antiretroviral and anti-inflammatory drugs targeting the central nervous system. Platelet-activating factor, a mediator of inflammation, is an HIV-induced neurotoxin secreted in the infected brain. In this work, we developed piperazine derivatives bearing a heterocyclic moiety as PAF-antagonists and HIV-1 replication inhibitors with micromolar potency.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Fármacos Anti-VIH/síntesis química , Demencia/prevención & control , Piperazinas/farmacología , Factor de Activación Plaquetaria/antagonistas & inhibidores , Fármacos Anti-VIH/farmacología , Demencia/etiología , Relación Dosis-Respuesta a Droga , VIH-1 , Humanos , Piperazinas/síntesis química , Relación Estructura-ActividadRESUMEN
HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS dementia complex. We previously reported that a trisubstituted piperazine derivative is able to diminish both HIV-1 replication in monocyte-derived macrophages and PAF-induced platelet aggregation. We report in this work new compounds obtained by modifying its piperazine substituents. The structure-activity relationship study shows that a better dual activity or even pure antiretroviral compounds can be obtained in this series.