RESUMO

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.

Assuntos

Inativadores do Complemento/química , Proteínas do Sistema Complemento/química , Sesquiterpenos/química , Inativadores do Complemento/síntese química , Inativadores do Complemento/farmacologia , Proteínas do Sistema Complemento/metabolismo , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade