Cytotoxic and Anti-Inflammatory Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

Abstract

Five new eunicellin-based diterpenoids, krempfielins E–I (1–5) and seven known compounds (6–12) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis. Metabolites 5, 6, 10 and 12 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 6 and 10 could potently inhibit the accumulation of the pro-inflammatory iNOS protein, and 6 and 12 could significantly reduce the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.

Krempfielins J-M, New Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

“…NMR spectroscopic data of 1 (Table 1) showed the presence of one acetoxy group (δ C 169.6 and 22.4; δ H 2.12, s, 3H) and one methoxyl group (δ C 57.0 and δ H 3.34, 3H, s). The NMR data of 1 was found to be similar to the known compound, 7 [22,25] (Chart 1). Comparison of the NMR data of them revealed that the only difference between both compounds arises from the replacement of the n -butyryloxy group at C-3 in 7 by one acetoxy group in 1 .…”

“…The soft coral Cladiella krempfi has been found to generate several types of metabolites including eunicellin-type diterpenoids [16,17] and pregnane-type steroids [18,19,20]. Our previous study on the bioactive secondary metabolites of a Taiwanese soft coral Cladiella krempfi also resulted in the isolation of a series of new eunicellin-based diterpenoids, krempfielins A–I [21,22]. In this paper, we further report the discovery of four new eunicellin-based diterpenoids, krempfielins J–M ( 1 – 4 ), along with two known diterpenoids sclerophytin F ( 5 ) [23] and litophynol B ( 6 ) [24] (Chart 1).…”

Krempfielins Q and R, Two New Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

“…The relative configuration of 1 was thus established. Comparison of the 1 H and 13 C NMR spectroscopic data of 1 with those of its 7,16-dehydration derivative, krempfielin E ( 4 ) [ 16 ], further confirmed the structure of 1 .…”

“…Soft corals of the genus Cladiella have been known to be rich sources of eunicellin-type metabolites and several bioactivities of these compounds have been studied [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Our previous studies on the soft coral Cladiella krempfi have resulted in the isolation of a series of new eunicellin-based diterpenoids, krempfielins A–P [ 15 , 16 , 17 , 18 ]. Our contineous investigation on the chemical constituents of soft coral C .…”

“…krempfi has afforded two new compounds, krempfielins Q and R ( 1 and 2 in Chart 1 ), and one minor known compound cladieunicellin K ( 3 ) [ 11 ]. The molecular structures of 1 and 2 , including the relative configurations, were established by the detailed spectroscopic analysis and by comparison with related physical and spectral data of known compound, krempfielin E ( 4 ) [ 16 ]. For the anti-inflammatory activity of these two new compounds to inhibit the superoxide anion generation and elastase release in N -formyl-methionyl-leucyl phenylalanine/cytochalasin B (FMLP/CB)-induced human neutrophils and the cytotoxicity of them against five human cell lines, human T cell lymphoblast-like cell line (CCRF-CEM), human erythromyeloblastoid leukemia (K562), human acute lymphoblastic leukemia cell line (Molt 4), human ductal breast epithelial tumor cell line (T47D) and human colorectal adenocarcinoma cell line (DLD-1) were also evaluated.…”