RESUMEN
Adenosine receptor antagonists are generally based on heterocyclic core structures presenting substituents of various volumes and chemical-physical profiles. Adenine and purine-based adenosine receptor antagonists have been reported in literature. In this work we combined various substituents in the 2, 6, and 8-positions of 9-ethylpurine to depict a structure-affinity relationship analysis at the human adenosine receptors. Compounds were rationally designed trough molecular modeling analysis and then synthesized and evaluated at radioligand binding studies at human adenosine receptors. The new compounds showed affinity for the human adenosine receptors, with some derivatives endowed with low nanomolar Ki data, in particular at the A2AAR subtype. The purine core proves to be a versatile core structure for the development of novel adenosine receptor antagonists with nanomolar affinity for these membrane proteins.
Asunto(s)
Antagonistas del Receptor de Adenosina A2/síntesis química , Antagonistas del Receptor de Adenosina A2/metabolismo , Purinas/síntesis química , Purinas/metabolismo , Receptor de Adenosina A2A/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Células CHO , Cricetulus , Humanos , Ligandos , Masculino , Modelos Moleculares , Estructura Molecular , Unión Proteica , Ensayo de Unión Radioligante , Ratas Wistar , Relación Estructura-ActividadRESUMEN
People living with HIV (PLHIV) in Cameroon often seek care from traditional health practitioners (THPs) and use medicinal plants (MP). Most MP, however, still lacks evidence for their efficacy and safety, and their use, often undisclosed to referring physicians, may interfere with standard therapies. Therefore, we conducted a survey of 247 PLHIV in Dschang to assess the determinants, prevalence and trend of MP use. Besides, we surveyed 16 THPs about the use of MP in PLHIV and HIV-related knowledge. 54.9% PLHIV declared using in total 70 plants, 91.3% users were satisfied with MP, and unwanted effects were reported in 2 cases. MP users were less educated than nonusers, had longer disease duration and were more often unemployed. Only 3 THPs used MP in PLHIV, and most of them had insufficient knowledge of HIV. Results may be useful for education on HIV and integration of traditional medicines with conventional therapeutics.
