Abstract
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.
| Original language | Japanese |
|---|---|
| Pages (from-to) | 595-606 |
| Number of pages | 12 |
| Journal | Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry |
| Volume | 73 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2015 |
| Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Organic Chemistry
Cite this
Development of novel and characteristic biologically-active molecules based on natural products : Synthesis and biological functions of cage-shaped structure of physalins. / Hirai, Go.
In: Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, Vol. 73, No. 6, 01.06.2015, p. 595-606.Research output: Contribution to journal › Article
}
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 - 記事
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 -