青霉属真菌Penicillium sp.CPCC 400786的抗病毒活性成分

Antiviral chemical constituents from the fungus Penicillium sp. CPCC 400786

采用抗艾滋病毒抑制剂筛选模型对一株青霉属真菌Penicillium sp.CPCC 400786发酵产物的乙酸乙酯提取物进行活性评价,结果显示,其对艾滋病毒有较强的抑制活性。采用正相硅胶柱、Sephadex LH-20凝胶柱和半制备HPLC等色谱技术对乙酸乙酯提取物进行分离纯化,从中分离得到8个化合物。通过波谱数据分析,分别鉴定为:oxalicine A(1)、oxalicine B(2)、cis-4,6-dihydroxymellein(3)、亚油酸(4)、十八烯酸(5)、肉豆蔻酸(6)、尿嘧啶(7)、胸腺嘧啶(8)。化合物1和2为杂萜类化合物。对化合物1–6进行了抗艾滋病毒(HIV-1)和抗甲型流感病毒(H1N1)的活性评价。结果显示,化合物1具有良好的抗H1N1活性,其IC50值为38.5μmol/L,比阳性对照药利巴韦林稍弱(IC50=20.5μmol/L);化合物1和2具有抗HIV-1的活性,其IC50值分别为22.4、67.8μmol/L;其他化合物未显示抗病毒活性。本研究为从青霉属中发现更多抗病毒活性杂萜分子提供了依据。

The activity of ethyl acetate extract of the fungus Penicillium sp.CPCC 400786 was evaluated by using anti-HIV inhibitor screening model.The result showed that ethyl acetate extract presented a significant inhibiting effect on HIV.Eight compounds were separated and purified by silica gel column chromatography,Sephadex LH-20 column chromatography and preparative HPLC,and their structures were identified as oxalicine A(1),oxalicine B(2),cis-4,6-dihydroxymellein(3),linoleic acid(4),cis-9-octadecenoic acid(5),tetradecanoic acid(6),uracil(7),thymine(8)by analysis of spectroscopic data.Compounds 1 and 2 were meroterpene derivatives.Compounds 1–6 were evaluated for anti-HIV and anti-H1 N1 activities.Compound 1 displayed significant anti-H1 N1 activity with the IC50 value of 38.5μmol/L,and the activity was slightly weaker than that of positive control(ribavirin,IC50=20.5μmol/L).Compounds 1 and 2 showed anti-HIV activities with the IC50 values of 22.4 and 67.8μmol/L,respectively.Compounds 3–6 were inactive.More antiviral meroterpenoids from the genus Penicillium need further investigation.