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

在一种新型抗病毒化合物的筛选研究中，作者从褐藻马尾藻中发现了铬烯衍生物1和一些已知的质体醌。更仔细的分离发现，对HSV、HIV和HCMV具有较强抗病毒活性的化合物1是在分离过程中由已知的质体醌转化而来的伪产物；然而，这些质体醌即使对1型单纯疱疹病毒也没有抗病毒作用。作者开始用SAR方法寻找更有活性的类似于1的化合物，包括铬1的重塑、聚合物负载衍生物和与一些传递肽杂交的1的类似物。以这些质体醌和市售的简单化合物为原料，共合成了12个类似物。生物实验结果表明，由已知质体醌转化而来的4种铬对HSV-1、HSV-2、HCMV、流感和HIV的抗病毒活性与1种铬的活性相当。其余8种化合物在体外对HSV具有中等抗病毒活性。根据这些数据，染色体结构是表达抗病毒活性的关键。在HIV感染的原始分析中，这些染色质可能会抑制逆转录酶（RT）和一些趋化因子受体（如CCR5）。聚合物负载的铬的活性仍在研究中。此外，作者继续从藻类中发现新的生物活性化合物。从小红花中分离到4个新的抗氧化质体醌类化合物。不幸的是，这些新化合物没有表现出抗病毒作用。从与褐藻有关的其他褐藻中，获得了许多已知的化合物，如抗氧化类胡萝卜素（岩藻黄嘌呤的一种）、细胞毒性萜类和脂肪酸衍生物（甘油和氧脂类）。这些结果已经发表，见参考文献和专利。

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.