Efficient Semisynthesis of (-)-Pseudoirroratin A from (-)-Flexicaulin A and Assessment of Their Antitumor Activities.
Accumulating evidence indicates that naturalent-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 propertyin vitroandin vivo. However, this diterpenoid could merely be isolated in a limited amount from a rare source ofIsodon 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 fromI. flexicaulisin 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.
Department of Chemistry and Institute of Advanced Materials, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR China; School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. China.
Lei
L
Guo
School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR China.
Siu Wai
SW
Tsang
Department of Pharmacy, Liaocheng University , Shandong, China.
Tong-Xin
TX
Zhang
School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR China.
Kang-Lun
KL
Liu
School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR China.
Yi-Fu
YF
Guan
BioTools, Inc. , 17546 Bee Line Hwy, Jupiter, Florida 33458, United States.
Bo
B
Wang
State Key Laboratory of Phytochemistry and Plant Resources in West China, Chinese Academy of Sciences , Kunming, China.
Han-Dong
HD
Sun
School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR China.
Hong-Jie
HJ
Zhang
Department of Chemistry and Institute of Advanced Materials, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR China.
Man Shing
MS
Wong
(−)-Pseudoirroratin A; (−)-flexicaulin A; antitumor activity; apoptosis