An antiplasmodial new (bis)indole alkaloid from the hard coral Tubastraea sp.

Tubastarea sp., a stony coral (Dendrophylliidae) from the Great Hanish in the Archipelago of the Hanish Islands, Yemen, contains, in addition to the known aplysinopsin (1) and 6-bromo-3'-deimino-3'-oxoaplysinopsin (2), the new bis(indole) alkaloid (3). The structures of compounds (1-3) were elucidated by interpretation of spectral data. Compound 3 inhibits the growth of Plasmodium falciparum (chloroquine-resistant strain) with an IC(50) 1.2 microg mL(-1).

Short synthesis of 16beta-hydroxy-5alpha-cholestane-3,6-dione a novel cytotoxic marine oxysterol.

The first and short synthesis of 16beta-hydroxy-5alpha-cholestane-3,6-dione 1 a metabolite from marine algae, has been achieved in six steps from readily available diosgenin 5. Selective deoxygenation of primary alcohol of triol 6 has been accomplished in one step using Et(3)SiH and catalytic amount of B(C(6)F(5))(3) to produce compound 9 in high yield. Oxidation of 11 with PCC, allowed the introduction of 3,6-ene-dione functionality, and further catalytic hydrogenation and deprotection furnished the 3,6-diketo steroid 1.

3 Beta-(3,4-dihydroxycinnamoyl)-erythrodiol, a cytotoxic constituent of Zygophyllum geslini collected in the Algerian Sahara.

3beta-(3,4-Dihydroxycinnamoyl)-erythrodiol was isolated as the cytotoxic constituent of the roots of Zygophyllum geslini.

Purification and partial identification of novel antimicrobial protein from marine bacterium Pseudoalteromonas species strain X153.

A marine bacterium, X153, was isolated from a pebble collected at St. Anne du Portzic (France). By 16S ribosomal DNA gene sequence analysis, X153 strain was identified as a Pseudoalteromonas sp. close to P. piscicida. The crude culture of X153 was highly active against human pathogenic strains involved in dermatologic diseases, and marine bacteria including various ichthyopathogenic Vibrio strains. The active substance occurred both in bacterial cells and in culture supernatant. An antimicrobial protein was purified to homogeneity by a 4-step procedure using size-exclusion and ion-exchange chromatography. The highly purified P-153 protein is anionic, and sodium dodecylsulfate polyacrylamide gel electrophoresis gives an apparent molecular mass of 87 kDa. The X153 bacterium protected bivalve larvae against mortality, following experimental challenges with ichthyopathogenic Vibrio. Pseudoalteromonas sp. X153 may be useful in aquaculture as a probiotic bacterium.

Expression of MRF4 protein in adult and in regenerating muscles in Xenopus.

In Xenopus, previous studies showed that the transcripts of the myogenic regulatory factor (MRF) MRF4 accumulate during skeletal muscle differentiation, but nothing is known about the accumulation of XMRF4 protein during myogenesis. In this report, an affinity-purified polyclonal antibody against Xenopus MRF4 was developed and used to describe the pattern of expression of this myogenic factor in the adult and in regenerating muscles. From young forming myotubes, XMRF4 protein persistently accumulated in nuclei during the regeneration process and was strongly expressed in nuclei of adult muscles. No selective accumulation of XMRF4 protein was detectable at neuromuscular junctions, but XMRF4 immunoreactivity was observed in sole plate nuclei as well as in extrasynaptic myofiber nuclei. We also report that XMRF4 protein accumulated before the establishment of neuromuscular connections, showing that innervation is not necessary for the appearance of XMRF4 protein during muscle regeneration.

New sphingosines from the marine sponge Grayella cyatophora.

The marine sponge Grayella cyatophora furnished several new homologous sphingosines having the same acyl substituent. Structure elucidations were achieved by spectroscopic methods and chemical transformations.

Effects of toxic extracts and purified borbotoxins from Prorocentrum borbonicum (Dinophyceae) on vertebrate neuromuscular junctions.

Benthic dinoflagellates of the genus Prorocentrum are common in tropical and subtropical water and several species produce phycotoxins potentially involved in human toxic outbreaks. The toxic dinoflagellate Prorocentrum borbonicum collected at La Réunion Island (France) was cultured in laboratory. A crude extract of the organism displayed significant toxicity in mice characterized by progressive limb paralysis, severe dyspnea, and death, and the toxicity was retained, after partition, in the extract's butanol-soluble fraction (BSF). Electrophysiological experiments characterizing the fraction's effect on isolated vertebrate neuromuscular preparations revealed that it depolarizes the muscle membrane and reduces the driving force for endplate potentials (EPPs) evoked by nerve stimulation, blocking directly- and indirectly-elicited muscle twitches. The depolarization induced by P. borbonicum BSF was not due to Na(+) influx through voltage-dependent Na(+) channels, since tetrodotoxin neither prevented nor suppressed the depolarization. However, ouabain, a specific ligand of the Na/K ATPase, reduced the depolarization. These results suggest the presence of palytoxin-like compounds in the fraction. HPLC-MS and MS/MS analysis showed the presence of several toxins having identical UV absorbance, among which two new isomeric toxins, borbotoxin-A and -B, of molecular mass of 1037.6 Da were isolated. The purified borbotoxin-A, had no effect on the resting membrane potential of muscle fibers and did not affect directly-elicited muscle twitches. However, the toxin reduced nerve-evoked muscle twitches, in a dose-dependent manner, reduced EPPs' amplitudes and completely blocked miniature endplate potentials. These observations suggest that the main action of borbotoxin-A is to block post-synaptic nicotinic ACh receptors.

5,9,23-Triacontatrienoic methyl ester, an elastase inhibitor from the marine sponge Chondrilla nucula.

A polyethylenic fatty ester was isolated from the marine sponge Chondrilla nucula. The structure was elucidated through NMR spectral data and MS analysis as 5,9,23-triacontatrienoic methyl ester 1. Compound 1 is an elastase inhibitor [ID50 = 10 microg/mL (2 x 10(-5) M)].

Efficient Total Synthesis of (-)-Ilimaquinone.

The total synthesis of (-)-ilimaquinone, a metabolite isolated from sea sponges, is described. The key step of the synthesis is the attachment of the quinone moiety to the drimane skeleton. Alkylation of enone 11 obtained in four steps from the readily available diketone 8, with tetramethoxybenzyl bromide 15 as the alkylating agent, led to addition product 16 in excellent yield. The presence of the tetramethoxybenzyl group induced stereoselective hydrogenation of the exo olefin 18, leading to the required isomer in a 9:1 ratio. Treatment of compound 21 with ceric ammonium nitrate (CAN) afforded formation of the quinone and deprotection of only one methyl ether in one step to furnish the desired ilimaquinone 1.