Development of novel and characteristic biologically-active molecules based on natural products: Synthesis and biological functions of cage-shaped structure of physalins

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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 languageJapanese
Pages (from-to)595-606
Number of pages12
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume73
Issue number6
DOIs
Publication statusPublished - Jun 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

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title = "Development of novel and characteristic biologically-active molecules based on natural products: Synthesis and biological functions of cage-shaped structure of physalins",
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.",
author = "Go Hirai",
year = "2015",
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doi = "10.5059/yukigoseikyokaishi.73.595",
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