Isolation, structure elucidation, and biological activity of the steroid oligoglycosides and polyhydroxysteroids from the Antarctic starfish Acodontaster conspicuus

A total of 19 steroids, of which 13 steroidal oligoglycosides (nine new and four known) and six polyhydroxylated steroids (four new and two known), has been isolated from the Antarctic starfish Acodontaster conspicuus. The mixture is dominated by glycosides composed of steroidal aglycons having the hydroxyl groups typically disposed on one side of the tetracyclic nucleus, i.e., 3 beta,4 beta,6 alpha,8,15 beta-, with some having a sulfate at C-6, and differing in the side chains and/or in the disaccharide moieties that are usually attached at C-26, with some at C-28 and C-29. Those compounds are accompanied by minute amounts of glycosides with a delta 8(14)-double bond in the steroid, which is a structural feature not previously found among polyhydroxysteroids derived from starfish. Small amounts of six related unglycosidated polyhydroxysteroids and three higher-molecular-weight asterosaponins complete the composition of the mixture. The structures of the new compounds were determined by interpretation of their spectral data and by comparison with spectral data of known compounds. Eighteen of these compounds were evaluated for their ability to inhibit growth in Antarctic marine bacteria isolated from either the water column or the surfaces of benthic marine invertebrates. Of these compounds, 50% were active against at least one Antarctic marine bacterium. This suggests that these compounds may play an important role in deterring microbial fouling.     

Isolation and structure elucidation of cirensenosides O and P from the leaves of Oplopanax elatus Nakai

Among 1470 patients over 65-year-old who were treated for various diseases, 50 had gastric ulcer and 10 had duodenal ulcer. About half the gastric ulcers were located in the body and fundus (n = 24, 48.0%). One third of the patients with gastric or duodenal ulcers had as their chief complaints hematemesis and hematochezia (n = 20, 33.3%), and a greater number had atypical gastrointestinal complaints (general malaise, fever etc, n = 25, 41.7%). In 10 patients (16.7%) the ulcers were due to non-steroidal anti-inflammatory drugs, in 5 (8.3%) they were due to steroid hormones, both of which had been given to treat other conditions; in 45 (75.0%) the origin of the ulcers was unknown. Complications of gastric and duodenal ulcers were hematemesis and hematochezia (n = 20, 33.3%), and perforation (n = 2, 3.3%). Duodenal ulcers tended to be severe, and were associated with death due to bleeding and peritonitis.     

Purification from starfish eggs of a protein that depolymerizes actin

A protein which is capable of depolymerizing F-actin was purified from an extract of unfertilized starfish eggs by the use of DEAE-cellulose column chromatography and hydroxylapatite column chromatography. This protein has an apparent molecular weight of 17,000. It inhibited the extent of actin polymerization as well as depolymerizing F-actin rapidly. It was shown that this protein reacts with actin at a molar ratio of 1 : 1. The properties of this protein were compared with those of profilin from mammalian tissues.     

Isolation and partial structure determination of a clonidine-displacing substance from bovine lung and brain

A large scale extraction and isolation method was developed for the purification of clonidine-displacing substance (CDS) activity from bovine lung or brain. This optimised method used direct freeze drying of tissue, hexane removal of lipids, and methanol extraction of CDS activity. Using a bioassay directed isolation strategy a new CDS compound was purified from an extract of bovine lung. The isolation strategy involved subsequent steps of flash C-18 chromatography, ion exchange, size exclusion, and C-18 HPLC. An HPLC detection method was developed and applied to show that the new CDS is present in both lung and brain tissue. Spectroscopic data for this new CDS indicates that it is related to guanosine, but is not noradrenaline, adrenaline, histamine, agmatine, guanosine, GMP, GDP or GTP.     

Isolation and structure/activity features of halomon-related antitumor monoterpenes from the red alga Portieria hornemannii

Ten halogenated monoterpenes (2-6 and 8-12) related to the novel antitumor compound halomon (1) or to the carbocyclic analog 7 have been isolated from different geographic collections of the red alga, Portieria hornemannii. Structures were assigned to the basis of spectral analyses (primarily NMR and MS). The absolute configuration of isohalomon (2) was further established by X-ray crystallography. The compounds were comparatively evaluated alongside 1 and 7 in the U.S. National Cancer Institute's in vitro human tumor cell line screening panel. The results provide some interesting initial insights into the structure/activity relationships in this series.     

Isolation and structure elucidation of an intermediate in the photodegradation of ciprofloxacin

Ciprofloxacin decomposes photochemically in aqueous solutions at acidic pH forming two major degradation products. One of the products, isolated from irradiated solutions by flash chromatography, was 7-[(2-aminoethyl)amino]-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-3-quinoline carboxylic acid. The compound was an intermediate in the photochemical process, which degraded after longer exposure with a high-pressure mercury lamp to an aromatic amino-compound, 7-amino-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-3-quinoline carboxylic acid. The structure of the intermediate was elucidated on the basis of information from ultraviolet, mass and nuclear magnetic resonance spectra.     

Induction of germinal vesicle breakdown in a cell-free preparation from starfish oocytes

THE PERSISTENCE OF AIRWAY INFLAMMATION is believed to cause the mechanical changes and symptoms of asthma. After decades of research, a new class of medication has emerged that focuses on leukotrienes, mediators of inflammation. These substances are potent inducers of bronchoconstriction, increased vascular permeability and mucus production, and they potentiate the influx of inflammatory cells in the airways of patients with asthma. In this article the author reviews the development, mechanism of action, and clinical and toxic effects of the leukotriene synthesis inhibitors and receptor antagonists that are entering the North American market. These agents can decrease airway response to antigen, airway hyperresponsiveness and exercise-induced asthma. They are also effective inhibitors of ASA-induced symptoms. Although few published studies are available, the antileukotrienes seem almost as effective in the management of chronic asthma as low-dose inhaled corticosteroids, and their use permits a decrease in the frequency of use or dose of corticosteroids. Further evaluation and clinical experience will determine the position of targeted inhibition of the leukotriene pathway in the treatment of asthma.     

Electric fusion of unfertilized starfish oocytes

BACKGROUND: Local failure rates are high for locally irresectable primary or recurrent colorectal cancer, even when chemoradiation therapy is employed. AIM: This review evaluates evidence supporting aggressive preoperative chemoradiation followed by maximal surgical resection and intraoperative radiation therapy to achieve disease control and cure for patients with locally advanced irresectable primary or recurrent rectal cancer. RESULTS: A 5-year survival rate of 42 per cent with a central failure rate of 2 per cent may be achieved in patients with locally irresectable primary rectal cancer. In patients with locally recurrent disease, these values at 5 years are 18 and 28 per cent respectively. The 5-year incidence of distant metastasis remains high, affecting 64 per cent of patients with primary cancer and 75 per cent of those with recurrent cancer. CONCLUSION: A disease-free surgical resection margin remains paramount to achieve cure. Encouraging trends exist, however, for further evaluation of multimodality therapy as a means of reducing local recurrence of disease.     

Isolation, characterization, and sugar chain structure of endoPG Ia, Ib and Ic from Stereum purpureum

Three endopolygalacturonases (endoPG Ia, Ib, and Ic) were isolated from the culture filtrate of Stereum purpureum, the causative fungus of apple silver-leaf disease. Their properties, including specific activities, optimum pHs, thermal stabilities, and kinetic parameters (K(m) and Vmax) were compared. Their properties were very similar to one another except for the substrate specificity and relative molecular mass. The sugar chains of endoPG Is were released by hydrazinolysis, and one major sugar chain common to endoPG Is was isolated. The pyridylamino sugar was characterized by a two-dimensional mapping method using HPLC, and identified as a high mannose type N-linked sugar chain, Man alpha 1-6(Man alpha 1-3)Man alpha 1-6(Man alpha 1-3) Man beta 1-4 GlcNAc beta 1-4 GlcNAc (designated as M5.1). Observation of the course of Western blot analysis for the proteins from the culture filtrate with endoPG I antibodies showed that the fungus secreted three endoPG Is into the culture broth during the growing period.     

A new indole derivative from the red alga Chondria atropurpurea. Isolation, structure determination, and anthelmintic activity

Chondriamide C (3), a new bis(indole) amide, was isolated from the red alga Chondria atropurpurea, and its structure was established from spectroscopic data and chemical transformations. A new natural product, 3-indoleacrylamide (4), and the previously described chondriamides A and B (1, 2) and 3-indoleacrylic acid (5) were also isolated. The anthelmintic activities of compounds 1, 3, 4, and 6 (the O,N1,N1'-trimethyl derivative of compound 2) against Nippostrongylus brasiliensis in vitro were evaluated.     

Antineoplastic agents. 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (the Republic of Maldives)

The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 micrograms/mL) and 5 (1b, DU-145 prostate GI50 1.9 micrograms/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).