Research and Development of the New Antiviral Drugs by Remodeling of the New Diterpenoid Isolated from Sea Algae

在一种新的抗病毒化合物的筛选研究中，作者发现了褐藻马尾藻的色烯类化合物1和一些已知的质体素。更仔细的分离表明，化合物1对HSV、HIV和HCMV具有很强的抗病毒活性，是一种人工制品，是由已知的质醌在分离过程中转化而来的；然而，这些质醌即使对HSV-1也没有显示出抗病毒作用。作者开始用合成孔径雷达方法发现更多活性类似于1的化合物，包括色烯1、聚合物支载的衍生物以及1的类似物与一些递送肽杂交的重塑。以植物二酚类化合物和市售的简单化合物为原料合成了12个类似物。经生物活性测定，其中4个化合物对HSV-1、HSV-2、HCMV、流感和HIV的抗病毒活性与化合物1相当。其余8个化合物体外抗HSV活性较强。数据表明，色烯结构是表达抗病毒活性的关键。在HIV感染的初步分析中，这些色烯可能被抑制了逆转录酶和一些趋化因子受体，如CCR5。聚合物负载的色烯的活性仍在调查中。此外，作者还继续从藻类中寻找新的生物活性化合物。从密棘豆中分离得到4个与上述化合物相关的新的抗氧化质二酚。不幸的是，这些新化合物并没有表现出抗病毒的作用。从与米棘藻相关的其它褐藻中分离得到了许多已知的化合物，如抗氧化类胡萝卜素(岩藻黄嘌呤)、细胞毒性萜类化合物和脂肪酸衍生物(甘油酯和氧化脂类)。这些成果已经发表，请参阅参考文献和专利。

In the screening study for investigation of a new antiviral compound, the authors found the chromene derivative 1 from the brown alga Sargassum micracanthum along with some known plastoquinones. More careful isolation revealed compound 1 possessing a strong antiviral activity against HSV,HIV and HCMV to be an artifact, converted from the known plastoquinones in the isolation process ; however, these plastoquinones did not show antiviral effect even for HSV-1. The authors started to find much more active compound similar to 1 by SAR method, including the remodeling of chromene 1,polymer-supported derivatives and the analogs of 1 hybridized with some delivery peptides. Totally twelve analogs were synthesized from the plastoquinones and commercially available simple compounds. According to the bioassay of them, four chromenes converted from the known plastoquinones showed strong antiviral activity against HSV-1,HSV-2,HCMV, Influenza and HIV as much as that of 1. Moderate antiviral activity against HSV was observed from the remaining eight compounds in vitro. According to the data, the chromene structure is the crucial for expressing the antiviral activity. These chromenes might be inhibited reverse-transcriptase (RT) and some chemokine receptor such as CCR5 in the primitive analysis of HIV infection. The activity of polymer-supported chromenes were still under investigation. In addition, the author continued to find the new bioactive compounds from algae. Four new antioxidative plastoquinones related the above-mentioned ones were isolated from S.micracanthum. Unfortunately, these new compounds did not exhibit antiviral effect. From the other brown algae related S.micracanthum, a lot of known compounds were obtained such as antioxidative carotenoids (a kind of fucoxanthine), cytotoxic terpenoids and fatty acid derivatives (glycerides and oxylipins). These results were already published, and see the references and patent.