Antiasthmatic acetophenones — an in vivo study on structure activity relationship

Summary The recently isolated acetophenone glucoside androsin, as the major antiasthmatic principle of Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae), was used as a lead compound for detailed structure-activity relationship studies. More than 25 synthesized or commercially available acetophenones with modified substitution patterns were screened in the Plethysmographic guinea pig model using PAF and/or ovalbumin as challenging agents for the generation of bronchial constriction. Whereas the aglycones in most cases were more effective than the corresponding glycosides, substitution patterns in position 3 and 4 of the phenyl ring and the keto function attached to the phenyl ring were found to be essential for marked antiasthmatic effect. 3,5-Dimethoxy-4-hydroxy-acetophenone (acetosyringenin) showed the highest activity of all tested compounds. Initial in vitro studies on the mode of action could not sufficiently explain the mechanism of antiasthmatic activity.