抄録
We have focused on the design and creation of new biologically active molecules based on natural products or biomolecules. This article summarizes our synthetic approach towards the clarification of the mode-of-action of physalins, which are complex oxygenated steroidal natural products. Physalins consist of the typical plant-steroidal structure displayed in the AB-ring and the unique cage-shaped DEFGH-ring system present on the right side of the structures. As other plants steroids such as withanolides possess a similar AB-ring structure and sometimes exhibit similar biological activities, the AB-ring structure was considered to be relevant for their biological functions. We synthesized physalin analogues without the AB-ring structure in order to clarify the contribution of the right-side cage-shaped structure for the biological effect in physalins. Biological investigations using the synthesized analogues along with the natural products revealed that, among the analogues, PBright-4 showed moderate inhibitory activity towards NF-κB transcriptional activation, through a similar mode-of-action with physalin B, which possesses a double bond at the C5-C6 position. These results clearly indicated that the right-side partial structure of physalins plays a significant role in their biological activity.
