Relaxant effect of structurally related flavonoids on isolated tracheal rat rings: a SAR study

• Published in: Medicinal chemistry research 2018, Vol.27 (1), p.122-127
• Main Authors: Flores-Flores, Angélica, Hidalgo-Figueroa, Sergio, Villalobos-Molina, Rafael, Ibarra-Barajas, Maximiliano, Bazán-Perkins, Blanca, Navarrete-Vázquez, Gabriel, Estrada-Soto, Samuel
• Format: Article
• Language: English
• Subjects: Active control; Biochemistry; Biomedical and Life Sciences; Biomedicine; Carbachol; Cell Biology; Contraction; Flavonoids; Hydroxyl groups; Original Research; Pharmacology; Pharmacology/Toxicology; Substitutes; Theophylline
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-017-2055-y

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.