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

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。

Antiviral chemical constituents from the fungus Penicillium sp. CPCC 400786

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-H1N1 activities. Compound 1 displayed significant anti-H1N1 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.