Efficient Semisynthesis of (−)-Pseudoirroratin A from (−)-Flexicaulin A and Assessment of Their Antitumor Activities

Lei Guo, Siu Wai TSANG, Tong Xin Zhang, Kang Lun Liu, Yifu GUAN, Bo Wang, Han Dong Sun, Hongjie ZHANG*, Ricky M S WONG

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Accumulating evidence indicates that natural ent-kaurane diterpenoids show great potential for medical treatment of different pathological conditions including cytotoxicity, antibacterial, and anti-inflammatory activity. Among a variety of diterpenoids tested, (−)-pseudoirroratin A displayed a promising antitumor property in vitro and in vivo. However, this diterpenoid could merely be isolated in a limited amount from a rare source of Isodon pseudoirrorata. To overcome such scanty source, we developed a novel, facile, and efficient semisynthetic strategy to prepare (−)-pseudoirroratin A from natural (−)-flexicaulin A, which can be expediently obtained from I. flexicaulis in a great quantity. The three-dimensional structure and the absolute configuration of our synthetic diterpenoid have been determined and confirmed with the X-ray crystallographic analysis. More importantly, we demonstrated for the first time that pseudoirroratin A exerted significant cytotoxicity against human colorectal carcinoma cells via an induction of apoptosis, as well as a remarkable suppression on tumor growth in a colon cancer xenograft mouse model.

Original languageEnglish
Pages (from-to)372-376
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume8
Issue number3
DOIs
Publication statusPublished - 9 Mar 2017

Scopus Subject Areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

User-Defined Keywords

  • (−)-flexicaulin A
  • (−)-Pseudoirroratin A
  • antitumor activity
  • apoptosis

Fingerprint

Dive into the research topics of 'Efficient Semisynthesis of (−)-Pseudoirroratin A from (−)-Flexicaulin A and Assessment of Their Antitumor Activities'. Together they form a unique fingerprint.

Cite this