高等真菌中结构新颖和具有显著生物活性的次生代谢产物对于药物先导化合物的发现非常重要，而其中的杂合倍半萜因其结构为倍半萜和其它片段杂合形成，兼具倍半萜和杂合片段的活性潜质，能有效提高发现苗头分子的概率，继而为新化学实体药物的创制提供源泉。我们研究组近期陆续发现了有较高生物活性的该类新结构：地花菌素albaconol具有vanilloid receptor-1 (VR-1)受体拮抗作用（IC50 = 5 μM）；craterellin A对人的11beta-HSD2有显著抑制作用（IC50 = 1.5 μg/mL）。为了获得更多此类成分，继而开展系统深入的活性评价，本项目拟利用我国西南地区丰富的高等真菌资源为研究对象，重点分离鉴定杂合倍半萜类次生代谢产物，以期获得一系列新结构，丰富杂合倍半萜的结构类型，并利用各种酶、细胞筛选模型，从中寻找和发现高活性化合物。

Novel compounds found in higher fungi have significant biological activity and play a very important role in drug discovery. Among them, merosesquiterpenoids could increase the probability of finding potential active compounds. The structures of those chemical compositions containing biological characteristics of both sesquiterpenoid and heterozygous fragment, could be a boon to drug discovery. Our research group found new merosesquiterpenoids showed significant activity: albaconol, a antagonist to VR-1（IC50 = 5 μM）; craterellin A demonstrated strong inhibitory activities against human 11beta-HSD2 with IC50 value of 1.5 μg/mL. In order to obtaine a wide variety of merosesquiterpenoids, this project intends to take the advantage of the rich higher fungi resources in southwest China, focusing on isolation and structure elucidation of such metabolites from fruiting bodies and culture broth. Combination with using variety of enzymes and cell-based screening assays, we expect to found new structures which have supremely high active.