RESUMO
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.
Assuntos
Pró-Fármacos/química , Aminas/química , Doxorrubicina/química , Estrutura MolecularRESUMO
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.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Fármacos Anti-HIV/síntese química , Demência/prevenção & controle , Piperazinas/farmacologia , Fator de Ativação de Plaquetas/antagonistas & inibidores , Fármacos Anti-HIV/farmacologia , Demência/etiologia , Relação Dose-Resposta a Droga , HIV-1 , Humanos , Piperazinas/síntese química , Relação Estrutura-AtividadeRESUMO
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.