He K Q, Cheng G F, Xi F D, Guo Z R, Zhu X Y
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing.
Yao Xue Xue Bao. 1996;31(11):878-80.
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.
采用一种简单、可靠且高度灵敏的生物测定法，以致敏的豚鼠回肠纵行肌条来筛选过敏反应慢反应物质（SRS - A）的受体拮抗剂。研究了17种查耳酮的SRS - A受体拮抗活性。发现这些查耳酮中的大多数化合物在10⁻⁴ mol·L⁻¹浓度时具有SRS - A受体拮抗作用。其中，化合物5、13和17具有高效性，其IC₅₀分别为7.5×10⁻⁶、7.5×10⁻⁶和6.8×10⁻⁵ mol·L⁻¹。在相同条件下，已知的白三烯D₄受体拮抗剂FPL 55712的IC₅₀为3×10⁻⁴ mol·L⁻¹。看来化合物5、13和17的效力分别比FPL 55712高40倍、40倍和4.4倍。从查耳酮的构效关系分析，这些结果表明以下因素可能对SRS - A受体的活性拮抗剂很重要：（a）分子中存在π，π共轭体系；（b）查耳酮B环中的酯基比羧基更有利；（c）B环中羧基或酯基的间位或对位取代衍生物的拮抗作用比邻位取代化合物更强；（d）查耳酮A环中烷基的碳链长度对于1、4或6个碳原子比对于10或14个碳原子更有效。
