[Structure-activity relationship studies of chalcones as SRS-A receptor antagonists].
A simple, reliable and highly sensitive bioassay with sensitized longitudinal strips of guinea pig ileum was used for screening the receptor antagonists of slow reacting substance of anaphylaxis (SRS-A). The SRS-A receptor antagonistic activities of 17 chalcones were studied. Most compounds in these chalcones were found to have SRS-A receptor antagonistic action at the concentration of 10(-4) mol.L-1. Among them, compounds 5, 13 and 17 were highly effective with IC50s of 7.5 x 10(-6), 7.5 x 10(-6) and 6.8 x 10(-5) mol.L-1, respectively. Under the same conditions, the IC50 of FPL 55712, a known leukotriene D4 receptor antagonist, was shown to be 3 x 10(-4) mol.L-1. It would appear that compounds 5, 13 and 17 were 40, 40 and 4.4 times more potent, respectively, than FPL 55712. From analysis of structure-activity relationship of chalcones, these results suggest that the following factors may be important for an active antagonist of SRS-A receptors: (a) There is a system of pi, pi conjugation in the molecule; (b) The ester group in the B ring of chalcones is more favorable than the carboxyl group; (c) Antagonism for meta- or para-substituted derivatives of carboxyl or ester group in the B ring are more potent than ortho-substituted compounds; (d) The length of carbon chain of alkyl group in the A ring of chalcones is more effective for 1, 4 or 6 carbon atoms than for 10 or 14 carbon atoms.
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Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing.
Cheng
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Xi
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Guo
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Zhu
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D000818:Animals; D001681:Biological Assay; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D020024:Leukotriene Antagonists; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D013329:Structure-Activity Relationship
D020024:Leukotriene Antagonists; D002599:Chalcone