尖尾芋化学成分及其抗肿瘤活性研究  

Chemical constituents of Alocasia cucullate and their antitumor activities

作　　者：靳建杰 毛旭东 梁永枢[2] 胡晓[1] 颜仁梁[2] 黄春跃[1] JIN Jianjie;MAO Xudong;LIANG Yongshu;HU Xiao;YAN Renliang;HUANG Chunyue(National Key Laboratory of Lead Druggability Research,Shanghai Institute of Pharmaceutical Industry Co.,Ltd.,China State Institute of Pharmaceutical Industry Co.,Ltd.,Shanghai 201203,China;School of Pharmacy,Guangdong Food and Drug Vocational College,Guangzhou 510520,China)

机构地区：[1]中国医药工业研究总院有限公司,上海医药工业研究院有限公司,先导物成药性研究全国重点实验室,上海201203 [2]广东食品药品职业学院中药学院,广东广州510520

出　　处：《中草药》2024年第18期6123-6130,共8页Chinese Traditional and Herbal Drugs

基　　金：广东省中医药局科研项目(20221290);广东省医学科研基金项目(A2023416)。

摘　　要：目的对尖尾芋Alocasia cucullata的根茎进行化学成分及其抗肿瘤活性研究。方法采用80%乙醇加热回流提取,依次用二氯甲烷、醋酸乙酯、正丁醇萃取,用AB-8大孔吸附树脂、正相硅胶柱、ODS硅胶柱、Sephadex LH-20凝胶柱和制备型液相色谱对提取物进行分离纯化。根据化合物的波谱数据和理化性质进行结构鉴定。同时采用CCK-8检测法,以星形孢菌素(staurosporine,STSP)作为阳性对照,对化合物进行体外抗肿瘤活性实验。结果从尖尾芋根茎的80%乙醇提取物中分离鉴定出17个化合物,包括7个生物碱类、3个长链脂肪酸类、4个萜类、3个甾体类,分别鉴定为3-吲哚甲醛(1)、黄胡椒酰胺(2)、5-羟基-1H-吲哚-3-甲醛(3)、(3R,8aS)-六氢-3-(2-甲基丙基)吡咯并[1,2-a]吡嗪-1,4-二酮(4)、新刺孢曲霉素A(5)、N-顺式-阿魏酰酪胺(6)、N-反式-阿魏酰酪胺(7)、(–)-β-谷甾醇(8)、(22E)-麦角甾-6,9,22-三烯-3β,5β,8α-三醇(9)、(22E)-麦角甾-6,22-二烯-3β,5β,8α-三醇(10)、(S)-5-羟基-3,4-二甲基-5-戊基呋喃-2(5H)-酮(11)、地芰普内酯(12)、表-地芰普内酯(13)、蚱蜢酮(14)、苯十三烷酸(15)、(16Z)-16-十八烯-12,14-二炔酸(16)、(13S)-羟基-十八碳二烯酸(17)。化合物9和10对人乳腺癌MCF-7细胞半数抑制浓度(median inhibition concentration,IC50)值分别为32.13、31.49μmol/L。结论化合物1~3、9~17为海芋属首次分离,化合物4、5是尖尾芋首次分离得到。抗肿瘤活性实验结果表明,化合物9和10对MCF-7细胞具有增殖抑制作用。Objective To elucidate the bioactive substances in Alocasia cucullata and test their antitumor activities.Methods A 80%ethanol extract of A.cucullate was partitioned with dichloromethane(DCM),ethyl acetate(EtOAc),and n-butanol.The extracts were separated and purified by AB-8 macroporous adsorbent resin,positive phase silica gel column,ODS silica gel column,Sephadex LH-20 gel column,and preparative liquid chromatography.Their structures were identified by spectroscopic data and physiochemical properties.The compounds were subjected to evaluation of antitumor activities in vitro using CCK-8 assay with staurosporine(STSP)as the positive control.Results A total of 17 compounds,including seven alkaloids,three long-chain fatty acids,four terpenoids,and three steroids were isolated from the 80%ethanol extract of A.cucullate,and the structures were identified as indole-3-carboxaldehyde(1),aurantiamide(2),5-hydroxy-1H-indole-3-carboxaldehyde(3),(3R,8aS)-hexahydro-3-(2-methylpropyl)pyrrolo[1,2-a]pyrazine-1,4-dione(4),neoechinulin A(5),N-cis-feruloyl tyramine(6),N-trans-feruloyl tyramine(7),(-)-β-sitosterol(8),(22E)-ergosta-6,9,22-triene-3β,5β,8α-triol(9),(22E)-ergosta-6,22-diene-3β,5β,8α-triol(10),(S)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(11),loliolide(12),(+)-epi-loliolide(13),grasshopper ketone(14),benzenetridecanoic acid(15),(16Z)-16-octadecene-12,14-diynoic acid(16),and(13S)-hydroxyoctadecadienoic acid(17).Compounds 9 and 10 exhibited the inhibitory effects on human breast cancer MCF-7 cells with median inhibition concentration(IC50)values of 32.13,31.49μmol·L-1,respectively.Conclusion Compounds 1—3 and 9—17 were isolated for the first time from the genus Alocasia,and compounds 4 and 5 were isolated for the first time from this plant.The results of antitumor activity showed that compounds 9 and 10 had proliferation inhibition against human breast cancer MCF-7 cells.

关 键 词：尖尾芋 甾体类化合物 抗肿瘤 (22E)-麦角甾-6 9 22-三烯-3β 5β 8α-三醇 (22E)-麦角甾-6 22-二烯-3β 5β 8α-三醇 

分 类 号：R284.1[医药卫生—中药学]