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对拟层孔菌属中红缘拟层孔菌Fomitopsis pinicola和药用拟层孔菌F.officinalis子实体的7种羊毛甾烷型三萜类化合物fomitopsin C(1)、3-酮基-去氢硫色多孔菌酸(2)、去氢齿孔酮酸(3)、3-乙酰氧基-8,24-羊毛甾二烯-21-酸(4)、松苓酸A(5)、栓菌酸(6)和齿孔酸(7)进行了分离纯化;体外抗肿瘤方面,采用MTT法测试7种单体化合物对人乳腺癌MCF-7细胞、人宫颈癌Hela细胞、人肝癌Hep G2细胞和人肺癌A549细胞增殖的影响,结果表明7种化合物对MCF-7细胞较为敏感,对MCF-7半数抑制浓度IC50为2<5<4<1<3<6<7;体内抗肿瘤方面,采用H22荷瘤小鼠模型,对比研究体外抗肿瘤活性较好的化合物2~5对小鼠的影响,结果表明化合物2和化合物4抗肿瘤活性好,并呈现一定的剂量依赖关系,化合物2,4,5剂量为20 mg·kg~(-1)时的抑瘤率分别为65.31%,59.75%,58.72%,接近阳性药组的抑瘤率69.19%;近一步试验表明抗肿瘤作用与抑制VEGF表达和免疫调节相关,对细胞因子IL-4和IFN-γ表达的影响较大,与抗氧化作用关联性较少,根据结果推断出羊毛甾烷型四环三萜结构抗肿瘤构效关系可能为,在3位羟基被酮基或乙酰基取代和C环中15位连有羟基时,此类化合物的抗肿瘤作用增强。
Seven kinds of lanostane-type triterpenes, fomitopsin C (1), 3-keto-demethoxycinnamic acid (2), Hydrogen Perforated Acid (3), 3-Acetoxy-8,24-Lanosadien-21-Acid (4) Tramadol (6) and pericarp acid (7) were isolated and purified. In vitro anti-tumor, MTT assay of seven kinds of monomer compounds on human breast cancer MCF-7 cells, human cervical cancer Hela cells, human liver cancer Hep G2 cells and human lung cancer A549 cells. The results showed that the seven compounds were more sensitive to MCF-7 cells, the IC50 of MCF-7 was 2 <5 <4 <1 <3 <6 <7; In the aspect of H22 tumor-bearing mouse model, we compared the effect of compound 2 ~ 5 with good antitumor activity in vitro. The results showed that the antitumor activity of compound 2 and compound 4 was good and showed a certain dose-dependent relationship. Compound The antitumor rates of 2,4 and 5 were 65.31%, 59.75% and 58.72% respectively when the dosage was 20 mg · kg ~ (-1) and 69.19% With inhibition of VEGF expression and immunity The results showed that the anti-tumor structure-activity relationship of the lanostane-type tetracyclic triterpene structure may be deduced as follows: The antitumor effect of such compounds is enhanced when the hydroxyl group at the 3-position is substituted by a keto or acetyl group and the hydroxyl group at the 15-position of the C-ring.