Aquaculture Soft Coral Lobophytum crassum as a Producer of Anti-Proliferative Cembranoids.

Our continuous search for marine bioactive secondary metabolites led to the screening of crude extracts from a variety of aquaculture soft corals. The ethyl acetate (EtOAc) extract of Lobophytum crassum showed a distinctive chemical profile that was different from the wild type. It demonstrated significant anti-proliferative activity against Molt 4 leukemia cell with an IC50 value of 1 µg/mL after 24 h. Chemical investigation focusing on the unique peaks in L. crassum profile led to the discovery of a new α-tocopherol crassumtocopherol C (1), and two new cembrane-based diterpenoids culobophylins D (2) and E (3), along with ten known cembranoids (4-13). The structures of these isolates were elucidated using extensive spectroscopic techniques and a comparison with previously published data of related metabolites. Compound 2 was found to possess the first identified saturated internal C4-O-C14 linkage six-membered ring among all cembrane-type diterpenoids. The anti-proliferative activity of all the isolates (except 3) was evaluated against a limited panel of leukemia cell lines (Molt 4, K562, U937, and Sup-T1). The major compounds 8 and 10 exhibited the most anti-proliferative potent effect, with IC50 values ranging from 1.2 to 7.1 µM. The Structure Activity Relationship (SAR) of the isolates suggested that the presence of lactone moieties is crucial for the anti-proliferative activity against leukemia cells. Our work indicated that the development of an efficient aquaculture protocols for soft corals led to the discovery of new secondary metabolites with unique structural features. Such protocols can lead to a sustainable supply of biologically active compounds in enough quantities for the pharmaceutical industry.

Bioactive 6S-styryllactone constituents of Polyalthia parviflora.

Parvistones A-E (1-5), five new styryllactones possessing a rare α,ß-lactone moiety and a 6S configuration, were isolated from a methanolic extract of Polyalthia parviflora leaves. The structures and the absolute configuration of the isolates were elucidated using NMR spectroscopy, specific rotation, circular dichroism, and X-ray single-crystal analysis. Compounds 8, 9, 11, and 12 were isolated for the first time. The results were supported by comparing the data measured to those of 6R-styryllactones. Moreover, a plausible biogenetic pathway of the isolated compounds was proposed. The structure-activity relationship of the compounds in an in vitro anti-inflammatory assay revealed the 6S-styryllactones to be more potent than the 6R derivatives. However, the effect was opposite regarding their cytotoxic activity. In addition, 6S-styrylpyrones isolated showed more potent anti-inflammatory and cytotoxic activity when compared to the 1S-phenylpyranopyrones obtained.

Simplexins P-S, eunicellin-based diterpenes from the soft coral Klyxum simplex.

Four new eunicellin-based diterpenes, simplexins P-S (1-4), and the known compound simplexin A (5), have been isolated from the soft coral Klyxum simplex. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly 1D and 2D NMR experiments. Compounds 1 and 3-5 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines, 3 being the most cytotoxic.

Simplexins A-I, eunicellin-based diterpenoids from the soft coral Klyxum simplex.

Nine new eunicellin-based diterpenoids, simplexins A-I (1-9), were isolated from a Dongsha Atoll soft coral, Klyxum simplex. The structures of these compounds were established by detailed spectroscopic analysis (IR, MS, 1D and 2D NMR) and by comparison with the physical and spectral data of related known compounds. The absolute configuration of 1 was determined by a modified Mosher's method. Compounds 1, 4, and 5 were found to be cytotoxic toward a limited panel of cancer cell lines. Compound 5 was shown to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.

Induction of apoptosis by three marine algae through generation of reactive oxygen species in human leukemic cell lines.

In this study, we examined the antitumor effect of marine algae extracts on human hepatoma and leukemia cells. Ethyl acetate extracts from Colpomenia sinuosa (Cs-EA), Halimeda discoidae (Hd-EA), and Galaxaura oblongata (Go-EA) directly inhibited the growth of human hepatoma HuH-7 cells and leukemia U937 and HL-60 cells in a time- and dose-dependent manner. Specifically, these algae extracts induced apoptosis of U937 and HL-60 cells as evaluated by detection of hypodiploid cells using flow cytometry and observation of condensed and fragmented nuclei in algae extract-treated cells. Intracellular reactive oxygen species (ROS), especially hydrogen peroxide and superoxide anion, were increased about 2-3-fold in U937 cells treated with Cs-EA for 3-5 h. Interestingly, antioxidant N-acetylcysteine effectively blocked Cs-EA-, Hd-EA-, and Go-EA-induced apoptosis, suggesting that ROS is a key mediator in the apoptotic signaling pathway. In conclusion, our results show that algae extracts induce apoptosis in human leukemia cells through generation of ROS.

Glaucumolides A and B, Biscembranoids with New Structural Type from a Cultured Soft Coral Sarcophyton glaucum.

Glaucumolides A (1) and B (2), novel biscembranes composed of an unprecedented α,ß-unsaturated ε-lactone, along with the known metabolites ximaolide A (3) and isosarcophytonolide D (4), were isolated from the cultured soft coral Sarcophyton glaucum. The structures of the new metabolites were determined by extensive spectroscopic analyses. Compounds 1 and 2 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. In anti-inflammation assay, compounds 1 and 2 displayed strong inhibition of superoxide anion generation and elastase release in human neutrophils stimulated by fMLP/CB. Furthermore, both 1 and 2 were shown to significantly inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase protein, and compounds 1-3 were found to effectively reduce the expression of cyclooxygenase-2 protein, in lipopolysaccharide-stimulated RAW264.7 macrophage cells.

Steroids from the gorgonian Isis hippuris.

Six new polyoxygenated steroids, hippuristerones J-L (1-3), hippuristerols E-F (4, 5), and a novel gorgosteroid, 1alpha,3beta,5beta,11alpha-tetrahydroxygorgostan-6-one (6), were isolated from the gorgonian Isis hippuris. The structures of these metabolites were elucidated by extensive spectroscopic analyses and comparison of the NMR data with those of related steroids.

Briaexcavatolides S-V, four new briaranes from a Formosan gorgonian Briareum excavatum.

Four new briarane-type diterpenoids, briaexcavatolides S-V (1-4), have been isolated from a Formosan gorgonian Briareum excavatum. The structures, including the relative stereochemistry of these new metabolites, were established by extensive 1D and 2D NMR spectroscopic methods and by comparison of the related spectral data with those of known analogues.

Briarane derivatives from the gorgonian coral Junceella fragilis.

A new trihydroxyl briarane-type diterpenoid, junceellolide H (1), along with two known compounds, praelolide (2) and junceellin (3), have been isolated from the gorgonian coral Junceella fragilis. The structure, including the relative configuration of the new diterpenoid 1, was elucidated by extensive spectroscopic methods.