Search

In the search for potential new antiasthmatic drugs, the ex vivo relaxing effect and structural activity relationship (SAR) studies of a series of ten structurally related flavonoids were established. Also, glycosylated and prenylated flavonoids were included in this study in order to explore their relaxant effect. All flavonoids studied showed a significant relaxant effect on the contraction induced by carbachol (CCh) 1 µM on tracheal rat rings, with the exception of isoprenylated and glycosylated derivatives. Results indicated that the flavone scaffold or their 6-substituted or 7-substituted positions, exhibited best relaxant activity, being flavone ( 1), 6-hydroxyflavone ( 2), 6-aminoflavone ( 3), and 7-hydroxyflavone ( 6) the most active compounds, even more than the positive control (Theophylline). On the other hand, SAR analysis suggested that the presence of hydrogen-bond donor and acceptor substituents in position 6- or 7- in the flavone core, or the 2 and 3 double bond, and the increasing presence of hydroxyl groups in positions 4′-, 5′-, 6′-, and 6- could enhance the ex vivo relaxant effect of the flavonoids studied. Derived from SAR analysis, a pharmacophore mapping was proposed, taking into account the structure of 6-hydroxyflavone, in order to have the scaffold to show the best ex vivo relaxant activity. [ABSTRACT FROM AUTHOR]