Tetsuro Kawabata

Isolation of Antipodal (−)-Versicolamide B and Notoamides L−N from a Marine-Derived Aspergillus sp.

Antipodal (-)-versicolamide B and notoamides L-N were isolated from a marine-derived Aspergillus sp. The possible biosynthetic pathway of enantiomeric pairs of notoamide B and versicolamide B are proposed. Notoamide L is the first metabolite containing 25 carbons in the related prenylated indole alkaloids. Notoamide M is potentially a precursor to the proposed azadiene species involved in the putative intramolecular Diels-Alder reaction in the biogenesis of the bicyclo[2.2.2]diazaoctane ring system.

Acanthomanzamines A–E with New Manzamine Frameworks from the Marine Sponge Acanthostrongylophora ingens

Five new manzamine alkaloids, acanthomanzamines A-E, were isolated from the marine sponge Acanthostrongylophora ingens. Acanthomanzamines A and B are the first examples, containing a tetrahydroisoquinoline instead of a β-carboline in manzamine-related alkaloids. Acanthomanzamine C contains a hexahydrocyclopenta[b]pyrrol-4(2H)-one ring that may be converted from an eight-membered ring in manzamine A. Acanthomanzamines D and E have an additional oxazolidine and 2-methyloxazolidine rings, respectively, which fuse to the manzamine skeleton.

Acantholactam and Pre-neo-kauluamine, Manzamine-Related Alkaloids from the Indonesian Marine Sponge Acanthostrongylophora ingens

Two new manzamine alkaloids, acantholactam (3) and pre-neo-kauluamine (4), were isolated from the marine sponge Acanthostrongylophora ingens along with manzamine A (1) and neo-kauluamine (2). Acantholactam contains a γ-lactam ring N-substituted with a (Z)-2-hexenoic acid moiety and is proposed to be biosynthetically derived from manzamine A by oxidative cleavage of the eight-membered ring. Compound 4 was converted to the dimer 2 during storage, suggesting nonenzymatic dimer formation. Among the four isolated compounds, 1, 2, and 4 showed proteasome inhibitory activity.

Halenaquinone inhibits RANKL-induced osteoclastogenesis

Halenaquinone was isolated from the marine sponge Petrosia alfiani as an inhibitor of osteoclastogenic differentiation of murine RAW264 cells. It inhibited the RANKL (receptor activator of nuclear factor-κB ligand)-induced upregulation of TRAP (tartrate-resistant acid phosphatase) activity as well as the formation of multinuclear osteoclasts. In addition, halenaquinone substantially suppressed RANKL-induced IκB degradation and Akt phosphorylation. Thus, these results suggest that halenaquinone inhibits RANKL-induced osteoclastogenesis at least by suppressing the NF-κB and Akt signaling pathways.

Inhibitors for cholesterol ester accumulation in macrophages from Chinese cabbage

The cholesterol ester accumulates in macrophages in the early stage of atherosclerotic lesions, leading to the formation of foam cells. We examined the inhibitory effects of the crude extracts of 22 edible plants on foam cell formation and isolated nine chlorophyll derivatives as potent inhibitors from Chinese cabbage. The results of the present study suggest that the chlorophyll derivatives contained in edible plants may be useful for the prevention and treatment of atherosclerosis. Graphical abstract Nine chlorophyll derivatives were isolated from Chinese cabbage as potent inhibitors of the cholesterol ester accumulation in macrophages.

Enantioselective inhibitory abilities of enantiomers of notoamides against RANKL-induced formation of multinuclear osteoclasts

The marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus NRRL 35600 produce enantiomeric prenylated indole alkaloids. Investigation of biological activities of the natural and synthetic derivatives revealed that (-)-enantiomers of notoamides A and B, 6-epi-notoamide T, and stephacidin A inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenic differentiation of murine RAW264 cells more strongly than their respective (+)-enantiomers. Among them, (-)-6-epi-notoamide T was the most potent inhibitor with an IC50 value of 1.7μM.

1-Hydroxyethylhalenaquinone: A new proteasome inhibitor from the marine sponge Xestospongia SP

A new halenaquinone derivative, 1-hydroxyethylhalenaquinone (1), was isolated from the marine sponge Xestospongia sp. as a proteasome inhibitor together with three known compounds, halenaquinone (2) and 3-ketoadociaquinones A (3) and B (4). 1-Hydroxyethylhalenaquinone (1) was the first halenaquinone derivative containing an alkyl group at the keto-furan C-1 position. Compounds 1 and 2 inhibited the chymotrypsin-like activity of the proteasome with IC50 values of 0.19 and 0.63 μM, respectively, whereas 3 or 4, each containing a thiomorpholine 1,1-dioxide moiety, scarcely inhibited its activity, even at a concentration of 5 μM. Halenaquinone (2, Figure 1) is a pentacyclic compound that has been isolated from marine sponges. This compound and its derivatives are known to exhibit antimicrobial, antifungal, cytotoxic, and antimalarial activities and also inhibit various enzymes, such as v-Src tyrosine kinase, phosphoinositide 3-kinase (PI3K), Cdc25B phosphatase, RAD51 (homologous-paring activity), phospholipase A2, and farnesyltransferase. In our search for biologically active natural products, we found that the extract of the marine sponge Xestospongia sp. inhibited proteasome activity. We here described the bioassay-guided isolation of a new halenaquinone derivative, 1-hydroxyethylhalenaquinone (1, Figure 1), and 2 as proteasome inhibitors. HETEROCYCLES, Vol. 89, No. 11, 2014 2605