一种新型酯类甾体化合物的设计合成及其抗炎生物活性的研究

Synthesis and Evaluation of a New Kind of Ester Steroids Compounds with Anti-Inflammatory Bioactivities

目的:设计合成一种具有抗炎活性的新型酯类甾体化合物。方法:以孕烯醇酮为基本母核的取代醛和酮通过Clasien-Schmidt缩合反应合成查尔酮衍生物后和反式肉桂酸反应合成具有酯类结构的甾体化合物;其结构通过核磁氢谱、质谱、红外图谱确证;以RAW 264.7巨噬细胞为实验细胞株,通过硝酸还原酶法检测NO的浓度来评估其抗炎活性。结果:共设计合成3个新型酯类甾体化合物(b1~3),其中b2的抗炎效果最佳(IC_(50)=3.40μmol/L),其抑制脂多糖(LPS)诱导RAW 264.7巨噬细胞产生NO的效果随浓度的增大而增强;b2在体外抑制LPS诱导RAW 264.7巨噬细胞生成NO的效果与地塞米松相当。结论:新型酯类甾体化合物具有抑制炎症介质NO增长的作用,新型酯类甾体化合物b2具有良好的抗炎效果。

Objective： To design and synthesis of a novel ester steroidal derivatives with anti-inflammatory bioactivities. Methods： First, chalcone derivatives were obtained via the base-catalyzed Claisen-Schmidt condensation with corresponding pregnenolone and aromatic aldehydes. Chalcone derivatives with steroids and cinnamic acid reacted in methylene chloride to get ester steroid derivatives containing different substituents at the 17-position. After characterization by infrared（IR）, -1H-NMR, and MS, the target compounds were tested for their inhibitory activities of NO production in activated RAW 264.7 Macrophages to evaluate their antiinflammatory activities. Results： Three ester steroidal derivatives were synthesized, compounds b2 shows the superior anti-inflammatory activities（IC50=3.40 μmol/L）. b2 has a concentration dependency in inhibiting NO produced by LPS-activated RAW 264.7 Macrophages, and the effect of NO production decreases with increasing concentration; b2 almost shows the same effects to dexamethasone on the inhibitory activities of NO production in LPS-activated macrophages. Conclusion： The new ester steroid derivatives b1-3 has the effect of inhibiting the growth of inflammatory mediators NO; Compound b2 shows the best anti-inflammatory effect.