摘要
采用硅胶色谱法、重结晶法从椭圆嗜蓝孢孔菌Fomitiporia ellipsoidea子实体的石油醚提取物中分离得到4个甾类化合物,单体化合物通过与已知标准品比对确定化合物结构,分别为麦角甾醇(麦角甾-5,7,22-三烯-3β-醇)、麦角甾醇过氧化物(5α,8α-过氧麦角甾-6,22-二烯-3β-醇)、麦角甾-7,22-二烯-3β-醇-棕榈酸酯和麦角甾-4,6,8(14),22(23)-四烯-3-酮。采用MTT法检测甾类化合物对人肿瘤细胞的抑制活性。采用H22裸鼠移植模型法评价甾类化合物的体内抗肿瘤活性。结果表明:在细胞毒实验中,麦角甾醇和麦角甾醇过氧化物对人肝癌细胞株Hep G2、人乳腺癌细胞株MCF-7、人宫颈癌细胞株Hela和人肺癌细胞株A549均有较好的抑制活性,麦角甾醇效果最佳,在浓度为50·g/m L时抑制率分别达到82.89%、74.33%、50.03%和69.33%,IC_(50)值分别为20.61·g/m L、37.18·g/m L、49.89·g/m L和38.74·g/m L,对Hep G2的抑制能力优于其他细胞系。在体内实验中,麦角甾醇和麦角甾-4,6,8(14),22(23)-四烯-3-酮在剂量为50mg/kg/d时抑瘤率分别为60.75%和63.21%,并且麦角甾醇组瘤鼠的脾指数有显著增加。构效关系分析认为甾核的C-3位被羟基或羰基取代后,化合物的抗肿瘤活性较显著。
Four steroids, ergosterol （ergosta-S,7,22-triene-3β-ol）, ergosterol peroxide （5a,8a-epidioxyergosta-6,22-dien- 3β-ol）, ergosta-7,22-dien-3β-yl palmitate and ergosta-4,6,8（14）,22（23）-tetraen-3-one, were separated from petroleum ether extract of Fomitiporia ellipsoidea fruiting body by silica gel column chromatography and recrystallization. The structure was identified by NMR and MS, and compared with standardized product. The cytotoxicity of four steroids to HepG2, MCF-7, Hela and A549 cell lines were assessed with trypan blue method. In vivo tumor growth inhibition was assayed with H22 tumor mouse model. The cytotoxicity test results showed that ergosterol and ergosterol peroxide had better inhibition effects to HepG2, MCF-7, Hela and A549 cell lines, especially ergosterol whose inhibition rates to the four cell lines were 82.89%, 74.33%, 50.03% and 69.33% under the dose of 501μg/mL, and the ICs0 values were 20.61μg/mL, 37.28μg/mL, 49.89μg/mL and 38.74μg/mL respectively. The inhibitory activity of ergosterol on HepG2 was stronger than that on other tumor cell lines. The test results in vivo showed that the inhibition rates of ergosterol and ergosta-4,6,8（24）,22（23）-tetraen-3-one against Hep（32 were 60.75% and 63.22% respectively under the dose of 50mg/mL. The spleen index in H22 tumor mouse intragastric administration by ergosterol was increased significantly. The analysis showed that the structure-activity relationship of steroids against tumor activity was obvious after replacing with hydroxyl or carbonyl at C-3.
出处
《菌物学报》
CAS
CSCD
北大核心
2015年第2期293-300,共8页
Mycosystema
基金
国家自然科学基金(31270088)
长江学者和创新团队发展计划资助项目(IRT1134)
关键词
椭圆嗜蓝孢孔菌
甾类化合物
抗肿瘤活性
构效关系
Fomitiporia ellipsoidea, steroids, antitumor activity, structure-activity relationship
