Search for Bioactive Natural Products from Unexplored Medicinal Resources

在本研究中，我们利用未开发的海洋藻类、黏菌和热带植物等药用资源，构建了天然存在的小分子文库，并进行了筛选研究，寻找可能作为药物开发先导分子的生物活性物质。1)海洋生物：在渤索半岛采集了约100种海藻，并对其提取物进行了抑菌活性、盐藻毒性和胶原酶抑制活性检测。其中，分别从褐藻石重冈村（Ishige okamurae）和山马尾藻（Sargassum yamadae）中分离到一种绿单宁和一种抗菌质体醌。在渤索半岛共采集到裸鳃科植物30余种，并从皮鳃科植物中分离到新的萜类成分。2)黏菌：研究了日本野外采集的数百种黏菌的孢子萌发实验，并在实验室成功培养了几种黏菌的疟原虫，为天然产物化学研究提供了实际规模。结果，我们分别从培养的Didymium iridis、Physarum刚性绒泡菌和P.melleum疟原虫中分离到吡咯亚胺醌、多烯黄色素和肽内酯。此外，还从紫荆、念珠菌、casparyi管蝇和dimorphotheca管蝇的子实体中分别分离到一种新的抗菌萘醌、一种新的环蒽酰脯氨酸、一种细胞周期抑制双吲哚和一种细胞毒性三萜醛内酯。3)植物：研究了泰国孔敬地区近300种热带植物提取物的细胞毒性和细胞周期抑制活性筛选方案。其中，我们从蓝藻（Blumea glomerata, Compositae）中分离到一种具有细胞周期抑制活性的二萜，并对其绝对构型进行了修正。从龙舌兰科（Agavaceae）和姜黄科（Zingiberaceae）中分别获得了一个新的细胞毒性甾体六糖和一系列新的倍半萜二聚体。从夹竹桃科麻瓜中分离到一种新的对长春新碱耐药小鼠白血病P388细胞具有细胞毒活性的孕烷生物碱。少

In this study, we constructed a naturally-occurring small-molecule library using unexplored medicinal resources such as marine algae, myxomycetes, and tropical plants, and carried out a screening study searching for bioactive substances which may be expected as leading molecules for drug developments.1)Marine organisms : About 100 species of marine algae were collected at Boso Peninsula, and their extracts were examined against antimicrobial activity, Artemia salina toxicity, and collagenase inhibitory activity. Among them, a phlorotannin and an antimicrobial plastoquinone were isolated from brown algae Ishige okamurae and Sargassum yamadae, respectively. About 30 species of nudibranchs were also collected at Boso Peninsula, and new terpenoid constituents were obtained from Dermatobranchus otome.2)Myxomycetes : We studied spore germination experiments of hundreds of field-collected myxomycetes collected in Japan and succeeded in laboratory culture of plasmodia of several myxomycetes in … More a practical scale for natural products chemistry studies. As a result, we isolated pyrroloiminoquinones, polyene yellow pigments, and a peptide lactone from cultured plasmodia of Didymium iridis, Physarum rigidum, and P.melleum, respectively. A new antimicrobial naphthoquinone, new cycloanthranilylprolines, cell-cycle inhibitory bisindoles, and a cytotoxic triterpenoid aldehyde lactone were also isolated from field-collected fruit bodies of Cribraria purpurea, Fuligo candida, Tubifera casparyi, and Tubifera dimorphotheca, respectively.3)Plants : We investigated a screening program against cytotoxicity and cell-cycle inhibitory activity using almost 300 species of tropical plants extracts collected from Khon Kaen area of Thailand. Among them, we isolated a diterpene with cell-cycle inhibitory activity from Blumea glomerata (Compositae) and its absolute configuration was revised. A new cytotoxic steroidal hexasaccharaide and a series of new sesquiterpene dimers were obtained from Agave faurcroydes (Agavaceae) and Curcuma parviflora (Zingiberaceae), respectively. A new pregnane alkaloid with cytotoxic activity against vincristine-resistant murine leukemia P388 cells was isolated from Wrightia javanica (Apocynaceae). Less