TY - JOUR
T1 - Development of novel and characteristic biologically-active molecules based on natural products
T2 - Synthesis and biological functions of cage-shaped structure of physalins
AU - Hirai, Go
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
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U2 - 10.5059/yukigoseikyokaishi.73.595
DO - 10.5059/yukigoseikyokaishi.73.595
M3 - 学術誌
AN - SCOPUS:84955260363
VL - 73
SP - 595
EP - 606
JO - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
JF - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
SN - 0037-9980
IS - 6
ER -