Eunicellin-based Diterpenoids Research Articles

Coniferains A and B, new eunicellin-based diterpenoids from the octocoral Cladiella conifera (Tixier-Durivault, 1943)

Two new eunicellin-based diterpenoids, coniferains A ( 1 ) and B ( 2 ), have been isolated from the soft coral Cladiella conifera . Structures of eunicellins 1 and 2 were elucidated by spectroscopic analysis and the structure of a known eunicellin, australin G, was revised. • New eunicellin, coniferains A ( 1 ) and B ( 2 ), were obtained from an octocoral Cladiella conifera . • The structure of a known eunicellin, australin G, was revised. • Octocorallia belonging to genus Cladiella are proven to be rich sources of eunicellin-based diterpenoids.

The marine-derived pachycladin diterpenoids as novel inhibitors of wild-type and mutant EGFR

Epidermal growth factor receptor (EGFR) is a key player in proliferation and metastasis of various cancers. Discovery of novel EGFR inhibitors is still an urgent clinical oncology unmet need. Pachycladins are eunicellin-based diterpenoids isolated from the soft coral Cladiella pachycladous species. This study evaluated the anticancer activity of pachycladins A–E against diverse breast and cervical cancer cells. Pachycladin A (1) potently inhibited the proliferation of multiple cancer cell lines, without being cytotoxic to non-cancerous cells. The antiproliferative activity of 1 is mediated through cytostatic mechanisms rather than inducing apoptosis, as evidenced by lack of TUNEL response. Additionally, 1 arrested cell cycle in either G1 or G2/M phase, according to the cancer type, which induced caspase-dependent and independent apoptosis only after prolonged treatment. Meanwhile, 1 potently decreased microvessel formation and endothelial cell migration, suggesting its potential antiangiogenic activity. Different kinase profiling platforms revealed the exquisite potency and selectivity of 1 towards EGFR, even compared to other members of the EGFR family. In cancer cells, the antiproliferative activity of 1 was associated with suppression of EGFR activation and its downstream effectors. Interestingly, 1 significantly inhibited the drug-resistant T790M EGFR mutant, which is believed to be an attractive feature of EGFR inhibitors. Docking studies characterized the structural determinants required for efficient wild and mutant EGFR inhibition. Overlay studies of 1 with known EGFR inhibitors provided future guidance to chemically improve its binding affinity. Together, the anticancer activity of 1 is mediated by direct effects on tumor growth and angiogenesis, selectively via deactivating EGFR signaling, providing an excellent scaffold to control EGF-dependent cancers.

Two new eunicellin diterpenoids from the South China Sea gorgonian Muricella sibogae and their bioactivities

A systematic re-study on gorgonian Muricella sibogae from South China Sea yielded 10 eunicellin-based diterpenoids including two new ones, sibogins C and D (1 and 2). Their structures were elucidated by extensive spectroscopic analyses (1D and 2D NMR, IR and MS) and by comparison with data reported in literatures. All the isolates were tested for cytotoxic and antifouling activities. Compounds 3 and 5 showed significant antifouling activity against the green mussel Perna viridis, and especially 3 was suggested as a potent low-toxic antifouling agent with a large LC50/EC50 value of 18.6. This was the first report on the antifouling activity of the eunicellin-type diterpenoids against the green mussel.

Krempfielins Q and R, two new eunicellin-based diterpenoids from the soft coral Cladiella krempfi.

Two new eunicellin-based diterpenoids, krempfielins Q and R (1 and 2), and one known compound cladieunicellin K (3) have been isolated from a Formosan soft coral Cladiella krempfi. The structures of these two new metabolites were elucidated by extensive spectroscopic analysis. Anti-inflammatory activity of new metabolites to inhibit the superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (FMLP/CB)-induced human neutrophil cells and cytotoxicity of both new compounds toward five cancer cell lines were reported.

Two new eunicellin-based diterpenoids from the South China Sea gorgonian Muricella sibogae Nutting

Two new eunicellin-based diterpenoids, sibogins A (1) and B (2), along with one known analogue (3), and four known 9,10-secosteroids (4–7), were isolated from the gorgonian Muricella sibogae Nutting collected from the South China Sea. The structures of the new compounds were elucidated by comprehensive analysis of spectroscopic data, especially by using 2D NMR spectra. The antifouling activity on barnacle Balanus amphitrite and lethality towards brine shrimp Artemia salina of all the isolated compounds were evaluated.

Klymollins T-X, bioactive eunicellin-based diterpenoids from the soft coral Klyxum molle.

Five new eunicellin-based diterpenoids, klymollins T–X (1–5), along with two known compounds (6 and 7) have been isolated from the soft coral Klyxum molle. The structures of these new metabolites were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. Compound 5 was found to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. Furthermore, compounds 4 and 7 were shown to exhibit cytotoxicity against a limited panel of human cancer cell lines.

Eunicellin-based diterpenoids, hirsutalins N-R, from the formosan soft coral Cladiella hirsuta.

New eunicellin-type hirsutalins N–R (1–5), along with two known eunicellins, (6 and 7) were isolated from the soft coral Cladiella hirsuta. The structures of the metabolites were determined by extensive spectroscopic analysis. Cytotoxic activity of compounds 1–7 against the proliferation of a limited panel of cancer cell lines was measured. The in vitro anti-inflammatory activity of compounds 1–7 was evaluated by measuring their ability in suppressing superoxide anion generation and elastase release in fMLP/CB-induced human neutrophils.

Discovery of New Eunicellin-Based Diterpenoids from a Formosan Soft Coral Cladiella sp.

A new eunicellin diterpenoid, cladieunicellin I (1), and a new natural eunicellin, litophynin I diacetate (2), were isolated from a Formosan soft coral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods and by comparison of the spectral data with those of related analogues. Eunicellin 1 exhibited significant cytotoxicity toward the DLD-1 human colorectal adenocarcinoma cells.

Cladieunicellins K and L, New Eunicellin-Based Diterpenoids from an Octocoral Cladiella sp.

Two new eunicellin-based diterpenoids, cladieunicellins K (1) and L (2), were isolated from an octocoral Cladiella sp. The structures of 1 and 2 were elucidated by spectroscopic methods and 2 exhibited moderate cytotoxicity towards the MOLT-4 human leukemia.

Eunicellin-Based Diterpenoids from the Formosan Soft Coral Klyxum molle with Inhibitory Activity on Superoxide Generation and Elastase Release by Neutrophils

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 first eunicellin-based metabolite bearing a phenyl group and displays significant inhibition of both superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils.

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

New four eunicellin-based diterpenoids, krempfielins J–M (1–4) 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. The structure of compound 2 is rare due to the presence of the highly oxygenated pattern. Anti-inflammatory activity of 1–6 to inhibit the superoxide anion generation and elastase release in FMLP/CB-induced human neutrophils was also evaluated, and 2 and 4 were shown to possess the ability to inhibit the elastase release.

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

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.

Hirsutalins I–M, eunicellin-based diterpenoids from the soft coral Cladiella hirsuta

New eunicellin-base diterpenoids, hirsutalins I–M (1–5), were isolated from the soft coral Cladiella hirsuta. Their structures were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The absolute configuration of 2 was determined by Mosher's method. These compounds did not exhibit cytotoxicity toward a limited panel of cancer cell lines but showed nitric oxide inhibitory activity in LPS-stimulated RAW264.7 macrophage cells. Among them, compound 3 was found to possess the strongest NO inhibitory activity with an IC50 value of 9.8 μg/mL. Furthermore, 3 was shown to significantly reduce the expression iNOS protein in the same cells.

Polyoxygenated diterpenoids of the eunicellin-type from the Chinese soft coral Cladiella krempfi

A detailed chemical investigation of the Chinese soft coral Cladiella krempfi has yielded four new eunicellin-based diterpenoids along with five known compounds. The stereostructures of the new metabolites have been elucidated by extensive spectroscopic analysis, mainly based on 2D NMR spectroscopy, and by chemical transformations. A remarkable variation in the diterpene composition in dependence of the exact site of collection was observed. Some of the isolated diterpenoids were shown to exhibit antiproliferative activity against C6 glioma cells, multi-drug resistant tumor cell line.

Antifouling Eunicellin-Type Diterpenoids from the Gorgonian Astrogorgia sp.

Twelve new eunicellin-based diterpenoids, astrogorgins B-M (1-12), were isolated from a Chinese gorgonian Astrogorgia sp., together with ophirin, muricellin, astrogorgin, calicophirins A and B, and 14-deacetoxycalicophirin B. The structures of the new compounds were elucidated by extensive spectroscopic analysis and by comparison with data reported in the literature. Significant antifouling activity was observed for 14-deacetoxycalicophirin B against the larval settlement of the barnacle Balanus amphitrite at nontoxic concentrations with an EC(50) = 0.59 μg/mL, while the other analogues were effective within an EC(50) range of 5.14-17.8 μg/mL.

Klysimplexins U–X, Eunicellin-Based Diterpenoids from the Cultured Soft Coral Klyxum simplex

Abstract New eunicellin-based diterpenoids, klysimplexins U–X (1–4), were isolated from a cultured soft coral Klyxum simplex. Their structures were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The absolute configuration of 2 was determined by Mosher’s method. Compounds 1 and 2 are the first example of 4-oxygenated eunicellin-type diterpenes isolated from soft corals of this genus.

Bioactive Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

Four new eunicellin-based diterpenoids, krempfielins A–D (1–4), along with two known compounds (5 and 6) have been isolated from a soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compounds 5 and 6 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 2, 3, 5 and 6 were shown to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells.

Klymollins A–H, Bioactive Eunicellin-Based Diterpenoids from the Formosan Soft Coral Klyxum molle

Eight new eunicellin-based diterpenoids, klymollins A-H (1-8), were isolated during the chemical investigation of the soft coral Klyxum molle from Taiwan waters. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 4 was determined by Mosher's method. Bioassays of the new metabolites showed that compounds 3-8 displayed significant in vitro anti-inflammatory activity by inhibiting the expression of the iNOS protein, and compounds 3, 4, and 6-8 also could effectively reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.

Simplexins J–O, Eunicellin-Based Diterpenoids from a Dongsha Atoll Soft Coral Klyxum simplex

Abstract Six new eunicellin-based diterpenoids, simplexins J–O (1–6), were isolated from a Dongsha Atoll soft coral, Klyxum simplex. The structures of these compounds were established by detailed spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compounds 4–6 have been found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein in LPS-stimulated RAW264.7 macrophage cells.

Cladielloides C and D: Novel Eunicellin-Based Diterpenoids from an Indonesian Octocoral Cladiella sp.

Abstract Chemical investigation on an Indonesian octocoral identified as Cladiella sp. has led to the isolation of two novel eunicellin-based diterpenoids, cladielloides C (1) and D (2). The structures of 1 and 2 were established by spectroscopic methods. Compound 1 exhibited significant cytotoxicity toward CCRF-CEM tumor cells and metabolites 1 and 2 displayed moderate inhibitory effects on superoxide anion generation by human neutrophils.