RESUMEN

A new series of tricyclic carboxylic acids with a 3H-spiro[benzofuran-2,10-cyclohexane] skeleton were synthesized from filifolinol, as analogs of the natural complement inhibitor K76-COOH. Their complement inhibitory activity was determined aiming to probe the importance of structural characteristics of the alicyclic part of K76-COOH. The presence and stereochemistry of O- and N-functionalities on C3' of the filifolinol derivatives are relevant for biological activity. The IC50 values of the most potent compounds were comparable or surpassed the activity of K76-COOH. The results also suggest that the diol moiety of the natural product may be useful for improving compound solubility.

Asunto(s)

Inactivadores del Complemento/química , Proteínas del Sistema Complemento/química , Sesquiterpenos/química , Inactivadores del Complemento/síntesis química , Inactivadores del Complemento/farmacología , Proteínas del Sistema Complemento/metabolismo , Sesquiterpenos/síntesis química , Sesquiterpenos/farmacología , Relación Estructura-Actividad