摘要
目的阐明深海来源曲霉16-02-1的代谢产物及其抗肿瘤抗真菌活性。方法采用活性跟踪模式,利用多种色谱技术分离纯化代谢产物,结合化学反应的理化及波谱数据鉴定化合物。采用MTT法测试抗肿瘤活性,纸片法测试抗真菌活性。结果从曲霉16-02-1产物中分离鉴定了新曲霉酸(1)、ferrineoaspergillin(2)、(2'S)-4-甲氧基-3-(2'-甲基-3'-羟基)丙酰基-苯甲酸甲酯(3)、黄曲霉素(4)、环(反式-4-羟基-L-脯氨酸-L-亮氨酸)(5)、环(反式-4-羟基-L-脯氨酸-L-苯丙氨酸)(6)、尿嘧啶(7)和(11S)-新羟基曲霉酸(8)等8个化合物。化合物1~8对人癌细胞K562、HL-60、HeLa、BGC-823有一定抑制作用,在100μg.mL-1浓度下对K562细胞的抑制率在33.6%~43.6%之间,1和8还对白色念珠菌和土曲霉表现出较弱抑菌活性。结论首次从深海来源真菌产物中分离得到化合物1~4和8,其中1为曲霉16-02-1的主产物,发酵产率28.8mg/L。首次报道3的2'S和8的11S绝对构型、8的13 C NMR数据及其在DMSO-d6和CD3OD中的1 H NMR数据、以及8在DMSO-d6中酮式―烯醇式互变异构的NMR证据。化合物2~4和8对部分人癌细胞的抑制活性亦首次测试报道。
Objective To investigate the metabolites of Aspergillus sp. 16-02-1 isolated from a deep sea sediment and test their antitumor and antifungal activities. Methods Separating operations were per- formed in a bioassay-guided manner using various chromatographic means. Compounds isolated were i- dentified on the basis of their physicochemical and spectroscopic data coupled with chemical reactions. Antitumor and antifungal activities were tested by MTT and paper-disc methods, respectively. Results Eight compounds 1-8 were isolated from the metabolites of Aspergillus sp. 16-02-1 and identified as neoaspergillic acid (1), ferrineoaspergillin (2), methyl (2S)-4-methoxy-3- (2-methyl-3-hydroxy) propi- onyloxy-benzoate (3), flavaeol (4), eyclo-(trans-4-hydroxy-L-prolyl-L-leucine) (5), cyclo-(trans-4-hy- droxyl-L-prolyl-L-phenylalanine) (6), uracil (7) and (11S)-neohydroxyaspergillic acid (8), respective- ly. Compounds 1-8 inhibited the growth of human cancer K562, HL-60, HeLa and BGC-823 cells to a certain extent and their inhibition rates on K562 cells ranged from 33.6% to 43.6% at 100 g mL-1. Compounds 1 and 8 also showed a weak antifungal activity on Candida albicans ATCC 10231 and As- pergillus terreus Thom var. terreus W-1. Conclusions Compounds 1 -4 and 8 were obtained from the metabolites of fungi from deep sea samples, for the first time, among which 1 was the major metabolite of strain 16-02-1, with the yield of 28. 8 mg/L. The 2S for 3 and 11S for 8 absolute configurations, the 13C NMR data of 8 together with its tH NMR data in DMSO-d6 and CD3OD, and the NMR evidence for the keto-enol tautomerism of 8 in DMSO-d6 were reported for the first time. The inhibitory effect of compounds 2-4 and 8 on several human cancer cell lines was also assayed for the first time. Key words: fungus from deep sea sediment; Aspergillus sp. 16-02-1; metabolite isolation and identifi- cation; antitumor activity; antifungal activity
出处
《中国海洋药物》
CAS
CSCD
北大核心
2013年第3期1-10,共10页
Chinese Journal of Marine Drugs
基金
国家自然科学基金(81172976
30973631)
国家高技术研究发展计划(2013AA092901)
国家科技重大专项(2012ZX09301-003)资助
关键词
深海来源真菌
曲霉16—02—1
代谢产物分离鉴定
抗肿瘤活性
抗真菌活性
fungus from deep sea sediment
Aspergillus sp. 16-02-1
metabolite isolation and identifi-cation
antitumor activity
antifungal activity