Naturally occurring marine brominated indoles are aryl hydrocarbon receptor ligands/agonists.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the toxic and biological effects of structurally diverse chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of a larger effort to identify the full spectrum of chemicals that can bind to and activate the AhR, we have examined the ability of several naturally occurring marine-derived brominated indoles and brominated (methylthio)indoles (collectively referred to as brominated indoles) to bind to the AhR and stimulate AhR-dependent gene expression. Incubation of mouse, rat, and guinea pig recombinant cell lines containing a stably transfected AhR-responsive luciferase reporter gene with eight brominated indoles revealed that all compounds stimulated luciferase reporter gene activity, although some species-specific differences were observed.

Four new polyoxygenated gorgosterols from the gorgonian Isis hippuris.

Four new polyoxygenated steroids (1-4) together with four known ones (5-8) have been isolated from the gorgonian Isis hippuris. The structures of the new compounds have been elucidated by spectroscopic analysis and chemical conversion. All of the new steroids showed moderate cytotoxicity against cultured NBT-T2 cells.

Deoxymanoalides from the nudibranch Chromodoris willani.

Two sesterterpenes, deoxymanoalide (1) and deoxysecomanoalide (2), were isolated from the nudibranch Chromodoris willani collected in Okinawa and their structures determined on the basis of spectroscopic data and chemical conversions. The mollusk feeds on a sponge containing manoalide (3) and secomanoalide (4) and is likely to biotransform them into 1 and 2. Both 1 and 2 showed moderate antimicrobial activity against Escherichia coli and Bacillus subtilis and inhibited snake venom phospholipase A2 at 0.

Synthesis of carbamate derivatives of iejimalides. Retention of normal antiproliferative activity and localization of binding in cancer cells.

The syntheses of six iejimalide carbamate derivatives are described. Their biological activity and those of the unmodified iejimalides A and B against breast and prostate cancer cell lines were determined. These results show that the serine hydroxyl group of iejimalides A and B is a permissive site that can be functionalized to form carbamate derivatives without significant loss of normal biological activity.

Polybrominated diphenyl ethers from the Indonesian sponge Lamellodysidea herbacea.

Four new (1-4) and 10 known polybrominated diphenyl ethers (5-14) have been isolated from the title sponge. The structures of the new entities were elucidated by interpretation of spectroscopic data and chemical transformations. These metabolites showed potent antimicrobial activity against Bacillus subtilis and moderate/weak cytotoxicity against NBT-T2 rat bladder epithelial cells.

Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A.

RNA helicases are molecular motors that are involved in virtually all aspects of RNA metabolism. Eukaryotic initiation factor (eIF) 4A is the prototypical member of the DEAD-box family of RNA helicases. It is thought to use energy from ATP hydrolysis to unwind mRNA structure and, in conjunction with other translation factors, it prepares mRNA templates for ribosome recruitment during translation initiation.

Terpenoids from Laurencia luzonensis.

Luzodiol (4), a diterpene possessing a new carbon skeleton, and five new sesquiterpenes (5-9) of the snyderane class have been isolated from the red alga Laurencia luzonensis and their structures determined by spectroscopic analysis. The relative stereochemistry of the known luzonensol (3) was assigned by its conversion to palisadin B (10).

Briarane diterpenes from two species of octocorals, Ellisella sp. and Pteroeides sp.

Eight new briarane diterpenes (1-4, 7-10) have been isolated from two species of octocorals and the structures elucidated by spectroscopic analysis. Two diterpenes (2, 3) from the gorgonian Ellisella sp. inhibited cytokinesis, causing multinuclei formation on NBT-II cells, while a known briarane (12) from the sea pen Pteroeides sp.

New cytotoxic furanosesterterpenes from an Okinawan marine sponge, Ircinia sp.

Five new sesterterpenes have been isolated from a lipophilic extract of a sponge, Ircinia sp., and their structures elucidated by spectroscopic and chemical methods. The absolute configurations of two metabolites (1, 3) were established by chemical degradation.

New scalarane class sesterterpenes from an Indonesian sponge, Phyllospongia sp.

A series of scalarane class sesterterpenes (1-8) have been isolated from an Indonesian sponge, Phyllospongia sp. Their structures were determined by spectroscopic analysis and confirmed by single-crystal X-ray diffraction on compound 1. The absolute stereochemistry of 1 was established by modified Mosher's method.

Bitungolides A-F, new polyketides from the Indonesian sponge Theonella cf. swinhoei.

Six new polyketides, bitungolides A-F (1-6), have been isolated from the Indonesian sponge Theonella cf. swinhoei and their structures elucidated by spectroscopic data and X-ray diffraction analysis. The bitungolides are a new class of Theonella metabolites that inhibit dual-specificity phosphatase VHR.

Araguspongines K and L, new bioactive bis-1-oxaquinolizidine N-oxide alkaloids from Red Sea specimens of Xestospongia exigua.

In addition to the previously reported (+)-araguspongine A, (+)-araguspongine C, (+)-araguspongine D, (-)-araguspongine E, and (+)-xestospongin B, two new N-oxide araguspongines, (+)-araguspongine K and (+)-araguspongine L, are described here. Their structures were established on the basis of spectral analyses including (1)H-(15)N HMBC. The promising in vitro antimalarial and antituberculosis activities of araguspongine C are reported.

Pachastrissamine, a cytotoxic anhydrophytosphingosine from a marine sponge, Pachastrissa sp.

An anhydrophytosphingosine named pachastrissamine (3) has been isolated as a cytotoxic principle of a sponge, Pachastrissa sp., and the structure including the absolute configuration determined by spectroscopic and chemical analysis.

The new anti-actin agent dihydrohalichondramide reveals fenestrae-forming centers in hepatic endothelial cells.

Background: Liver sinusoidal endothelial cells (LSECs) react to different anti-actin agents by increasing their number of fenestrae. A new structure related to fenestrae formation could be observed when LSECs were treated with misakinolide. In this study, we investigated the effects of two new actin-binding agents on fenestrae dynamics.

Cyclotheonamide E4 and E5, new potent tryptase inhibitors from an Ircinia species of sponge.

Tryptase is a protease released from mast cells and is believed to contribute to the inflammatory process in allergic diseases including asthma. In the course of screening to find tryptase inhibitors, we isolated two new tryptase inhibitors, cyclotheonamide E4 (3) and E5 (4), from a marine sponge of the genus Ircinia. The structures of these molecules were determined by interpretation of 1H and 13C NMR spectra, and they were shown to be closely related to the previously reported cyclotheonamides E (1), E2, and E3 (2).