Eunicellin-Based Diterpenoids from the
Formosan Soft Coral Klyxum
molle with Inhibitory Activity on Superoxide
Generation and Elastase
Release by Neutrophils
Ming-Chang Lin,
†,▽Bo-Wei Chen,
†,▽Chiung-Yao Huang,
†Chang-Feng Dai,
‡Tsong-Long Hwang,
§and Jyh-Horng Sheu*
,†,⊥,∥†Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan, Republic of China
‡Institute of Oceanography, National Taiwan University, Taipei 112, Taiwan, Republic of China
§Graduate Institute of Natural Products, Chang Gung University, Taoyuan 333, Taiwan, Republic of China
⊥Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan, Republic
of China
∥Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Republic of China
*
S Supporting InformationABSTRACT: Eleven new eunicellin-based diterpenoids possessing a cladiellane skeleton with a C-2, C-9 ether bridge,
klymollins I−S (1−11), have been isolated from the EtOAc extract of the soft coral Klyxum molle from Taiwan waters. The structures of compounds 1−11 were elucidated by extensive spectroscopic analysis, including 2D NMR spectroscopy (COSY, HSQC, HMBC, and NOESY). Compound 5
exhibited cytotoxicity toward several cancer cell lines. Compound 5 is the frst eunicellin-based metabolite bearing
a phenyl group and displays signifcant inhibition of both superoxide anion generation and elastase release in
O
ur previous chemical investigations of soft corals of the genus Klyxum and Cladiella have aforded severaleunicellin-based diterpenoids, of which some have exhibited interesting bioactivities.1−11 In order to discover novel and bioactive substances from marine invertebrates, the chemical constituents of the soft coral Klyxum molle, which has been previously investigated as Alcyonium molle,12 were further studied. During the course of our initial investigation of new substances from K. molle, eight eunicellin-type natural products, klymollins A−H, were discovered.9 In this paper, we report our continuing chemical investigation of this organism. This study led to the isolation, structure determination, and biological activity of 11 additional eunicellin metabolites, klymollins I−S (1−11), from more polar fractions of the soft coral extract. The structures of 1−11 were established by extensive spectroscopic analysis, including 2D NMR (COSY, HSQC, HMBC, and
NOESY) spectroscopy. The cytotoxicies of metabolites 1−11 against a variety of human tumor cell lines including human
erythro myeloblastoid leukemia (K562), human acute lymphoblastic leukemia (Molt-4), and human breast carcinoma
(T47D) were investigated. The abilities of 1−11 to inhibit
superoxide anion generation and elastase release in fMLP/CBinduced human neutrophils were also evaluated.
Received: May 8, 2013
