Department of Chemistry; School of Chinese Medicine
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.
(−)-flexicaulin A, (−)-Pseudoirroratin A, antitumor activity, apoptosis
Source Publication Title
ACS Medicinal Chemistry Letters
American Chemical Society
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acsmedchemlett.7b00033.
This work was supported by grants from the Hong Kong Baptist University (HKBU) Interdisciplinary Research Matching Scheme (RC-IRMS/12-13/03), the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKBU 12103014), and the Faculty Research Grants, Hong Kong Baptist University (FRG2/14- 15/047 and FRG1/15-16/020).
Link to Publisher's Edition
Guo, L., Tsang, S., Zhang, T., Liu, K., Guan, Y., Wang, B., Sun, H., Zhang, H., & Wong, M. (2017). Efficient semisynthesis of (−)-pseudoirroratin A from (−)-flexicaulin A and assessment of their antitumor activities. ACS Medicinal Chemistry Letters, 8 (3), 372-376. https://doi.org/10.1021/acsmedchemlett.7b00033
Additional FilesJA-5193-29188_suppl.pdf (1275 kB)