Chiral cruciferous phytoalexins: preparation, absolute configuration, and biological activity

Synthesized by an efficient one-pot spirocyclization method, two chiral cruciferous phytoalexins, 1-methoxyspirobrassinin (2) and 1-methoxyspirobrassinol methyl ether (4a), were prepared through optical resolution using the chiral HPLC method of corresponding racemates. The absolute configuration of natural (+)-2 was elucidated as R by using the direct comparison of ECD and VCD spectra with those of known (S)-(-)-spirobrassinin (1). Another chiral phytoalexin, (-)-4a, had its absolute configuration 2R,3R elucidated through the comparison of observed and calculated VCD. Interestingly, the absolute configurations of natural (S)-(-)-spirobrassinin (1) and (R)-(+)-1-methoxyspirobrassinin (2) were opposite of each other, even though their structures are almost similar, with the exception of an N-methoxy group. A significant difference in the antiproliferative activity between (2R,3R)-(-) and (2S,3S)-(+)-4a was observed.     

Chiral combinatorial preparation and biological evaluation of unique ceramides for inhibition of sphingomyelin synthase

Enantiomers or diastereomers of chiral bioactive compounds often exhibit different biological and toxicological properties. Here, we report the efficient synthesis of four stereoisomers of sphingosine and derivatization of unique chiral ceramides through a combinatorial chemistry by solid-phase activated resin ester. In addition, to test the effectivity of stereochemistry of ceramide, we demonstrated a cell-based assay of sphingomyelin synthase inhibition in the presence ofchiral unique ceramides, which suggested that libraries of this sort will be a rich source of biologically active synthetic molecules.     

Chiral C3 epoxides and halohydrins: Their preparation and synthetic application

Epichlorohydrin, 3-chloro-1,2-propanediol and glycidol are versatile chiral C3 syntons in organic synthesis. For the production of these, more efficient and more practical methods are required and many studies have been reported. In this review, biological and synthetic preparations of their synthons and microbial dehalogenation of halohydrins connected with the biological methods are described. Several of their synthetic applications are also introduced.     

Tea polyphenols-loaded nanocarriers: preparation technology and biological function

Biotechnology Letters - Tea polyphenols (TP) have various biological functions including anti-oxidant, anti-bacterial, anti-apoptotic, anti-inflammatory and bioengineered repair properties....     

Plant-based anticancer molecules: a chemical and biological profile of some important leads

A number of natural products, with diverse chemical structures, have been isolated as anticancer agents. Several potential lead molecules such as camptothecin, vincristine, vinblastine, taxol, podophyllotoxin, combretastatins, etc. have been isolated from plants and many of them have been modified to yield better analogues for activity, toxicity or solubility. Several successful molecules like topotecan, irinotecan, taxotere, etoposide, teniposide, etc. also have emerged as drugs upon modification of these natural leads and many more are yet to come. In this review, the authors have focused on four important anticancer leads, that is, camptothecin, taxol, combretastatin A-4 and podophyllotoxin. Their chemistry, structure and activity relationships, biological activities, modes of action, analogue synthesis and future prospects have been discussed.     

Evaluation of adaptogenic activity profile of herbal preparation

The herbal formulation, AVM is a proprietary formula that consists of extracts of herbs that have been used in Indian traditional medicine to promote physical and mental health, improve defense mechanisms of the body and enhance longevity. AVM (500 and 1000 mg/kg) was tested for its adaptogenic activity by determining antistress, anabolic and immunomodulatory effects. In antistress activity, pretreatment with AVM significantly attenuated the changes in ascorbic acid (from blood and adrenal), cortisol (from plasma and adrenal) and adrenal gland weights induced due to restrain stress (physical immobilization). Its antistress effect at 1000 mg/kg was comparable to that of diazepam (5 mg/kg) treated group. Leucopenia, and anemia induced by cyclophosphamide (CYP) was shown to reduce significantly by AVM. Treatment of AVM + CYP had increased spleen and thymus weights significantly as compared to CYP alone treated group. The anabolic activity was evaluated by weight gain of the levator ani muscle, ventral prostrate gland and seminal vesicles in rats as compared to untreated control.     

Preparation of biological samples in space: the experiment preparation unit

The Experiment Preparation Unit (EPU) is a facility that prepares biological samples for their upcoming experiment within Biolab (Columbus). For logistical reasons and to avoid the influence of the heavy launch loads and the microgravity environment before the actual initiation of the experiment, biological samples will be sent cryogenically frozen to the International Space Station. The Experiment Preparation Unit will prepare those samples by thawing and extracting the cryogenic fluid automatically after minimal crew intervention for set-up of the system. The EPU can be tele-operated directly from ground and consists of three major subsystems to guarantee its functionality: Functional Platform, Base and Control Panel.     

The preparation and biological activity of methyl 5,6-epoxy-retinoate

1. Oxidation of methyl retinoate with monoperphthalic acid gave methyl 5,6-epoxyretinoate, obtained as pale-yellow crystals, m.p. 89°. 2. The structure of the epoxide was confirmed by its ultraviolet, infrared, nuclear-magnetic-resonance and mass spectra. 3. The biological properties of the epoxide were investigated in male and female rats, and were found to be qualitatively similar to those of retinoic acid and methyl retinoate. 4. When administered to male rats reared on a vitamin A-free diet, the epoxide permitted growth although it did not maintain good general health. 5. Rats given a vitamin A-free diet and supplements of the epoxide had degenerate testes. 6. Female rats, maintained on a vitamin A-free diet containing retinoic acid and given supplements of the epoxide during pregnancy, resorbed their foetuses and failed to deliver litters. 7. The threshold of the electroretinogram response in male rats reared on a vitamin A-free diet with supplements of the epoxide was elevated above normal and was similar to that of rats maintained with methyl retinoate. 8. The oral administration of the epoxy acid to rats did not result in the accumulation of the corresponding epoxy alcohol in their livers.     

Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues

We describe a new class of NO-donor hypoglycemic products obtained by joining tolbutamide, a typical hypoglycemic sulfonylurea, with a NO-donor moiety through a hard link. As NO-donors we chose either furoxan (1,2,5-oxadiazole 2-oxide) derivatives or the classical nitrooxy function. A preliminary biological characterization of these compounds, including stimulation of insulin release from cultured rat pancreatic β-cells and in vitro vasodilator and anti-aggregatory activities, is reported.     

Conventional and long-circulating liposomes of artemisinin: preparation, characterization, and pharmacokinetic profile in mice

Artemisinin (qinghaosu), a unique endoperoxide sesquiterpene lactone isolated from Artemisia annua L., is a very active antimalarial drug, including severe and cerebral malaria. However, its therapeutical efficacy is limited due to its scarce bioavailability. In this article, artemisinin-loaded conventional and polyethylene glycol (PEGylated) liposomes were proposed as carriers to increase biopharmaceutical properties of the drug. Encapsulation efficacy was determined by high-performance liquid chromatography/diode array detection/electrospray ionization-mass spectrometry, dimensional analysis was performed by dynamic light scattering, and morphology was performed by trasmission electron microscopy. After dialysis, both liposomal formulations showed an encapsulation efficacy of more than 70%; mean diameter of all the artemisinin-loaded vesicles was approximately 130-140?nm. The polydispersity index of the formulations ranged from 0.2 to 0.3 and resulted as suitable for intraperitoneal (i.p.) administration. Pharmacokinetic profile and the main pharmacokinetic parameters of the carriers were evaluated in healthy mice i.p. Free artemisinin was rapidly cleared from plasma and hardly detected 1 hour after administration. Conversely, both liposomal formulations showed much longer blood-circulation time than free artemisinin; artemisinin was still detectable after 3 and 24 hours of administration, respectively, for conventional and PEGylated liposomes. AUC(0-24 h) values were increased by approximately 6 times in both of the liposomal formulations, in comparison with free artemisinin. A strong effect of formulation on the half-life of artemisinin was enhanced by more than 5-fold by the incorporation of PEG into liposomes. Liposomes loaded with artemisinin, especially the long-circulating vesicles, could really represent a new strategy for developing smart, well-tolerated, and efficacious therapeutic nanocarriers to treat tumors, but could also be very useful to treat parasitic disease.     

Undecagold clusters for site-specific labeling of biological macromolecules: simplified preparation and model applications

We report simple and rapid procedures for the synthesis of a variety of stable, water-soluble undecagold cluster, and model applications of a thiol-reactive gold cluster for the specific labeling of cysteine residues in proteins.     

Rosettes from Friend leukemia virus envelope: preparation and physicochemical and partial biological characterization.

Rosette-shaped particles mainly containing gp85 were isolated from Friend leukemia virus. The isolation procedure comprised lysis of the virion by Triton X-100, affinity chromatography on concanavalin A-Sepharose, and velocity sedimentation. The rosettes displayed a mean sedimentation constant of 32S and a buoyant density of 1.21 g/ml. They contained 1% Triton X-100 and about 2% phospholipid. gp85 was identified by polyacrylamide electrophoresis, staining with periodic acid-Schiff reagent, and immunoprecipitation with antisera against Friend leukemia virus gp71 and p15(E). Rosettes completely blocked the cytotoxicity of the gp71 antiserum. The ability to hemagglutinate was inhibited by antibodies to gp71.     

Large-scale preparation and biological activity of recombinant human parathyroid hormone

Human parathyroid hormone (hPTH) has been bacterially expressed in bioreactors as cro-β-galactosidase-hPTH fusion protein. We have developed a large-scale purification scheme that exploits the pH-dependent differential solubility of hPTH and a two-step Chromatographie procedure. We demonstrate that in a number of assay systems, the recombinant material obtained by this procedure is biologically active.     

Evaluation of in vivo biological activity profile of isoorientin

Anti-nociceptive, anti-inflammatory and gastroprotective activities of the known C-glycosyl flavonoid, isoorientin, were studied in rats and mice. For the anti-nociceptive activity assessment the p-benzoquinone-induced writing test, for the anti-inflammatory activity the carrageenan-induced hind paw edema model in mice, and for the gastroprotective activity the EtOH-induced ulcerogenesis model in rats were used. Isoorientin was shown to possess significant anti-nociceptive and anti-inflammatory activities at 15 mg/kg and 30 mg/kg doses, without inducing any apparent acute toxicity as well as gastric damage. However, the compound did not possess any significant gastroprotective activity against EtOH-induced ulcerogenesis.     

The preparation of pregnancy urine for an estrogen profile.

A method is described for purifying the estrogen content of pregnancy urine with little loss of the labile estrogens. The procedure makes use of the initial 50-fold purification effected by their precipitation whith ammonium sulphate, with simultaneous elimination of most urinary corticosteroids and 50--60% of urinary ketosteroids. It also employs the antioxident ascorbic acid as an additive in most stages of the procedure. The mild organic-solvent-HIO partition system of Brown is used for separating the strongly polar, 2including all "labile" estrogens, and of the weakly polar estrogens, from neutral steroids. The remaining neutral steroid still interfering with the assays were removed by an ascorbic acid treated ion exchange resin (AG 1). The final residues were revealed by mass-spectroscopy to consist almost solely of estrogens. Gas-liquid chromatography in which just 2 chromatograms are required yields a total of 12 "estrogen" peaks (for 12 estrogens which are excreted in amounts greater than 0.1 mg/day) in normal pregnancy urine, including all the known labile estrogens. Identification as estrogen for all but a few minor peaks of the gas chromatogram was obtained by mass-spectroscopy. The practical significance of the method lies in the fact that some labile estrogens are much more important in the estrogen metabolism of pregnant and nonpregnant women than heretofore generally thought.     

褐藻寡糖的制备方法及生物活性研究进展

褐藻胶是一类多糖聚合物,由于其独特的理化性质和有益健康的作用,已被广泛应用于制药和食品工业.然而,由于褐藻胶的水溶性低、黏度大,进而限制了褐藻胶的开发和应用.褐藻寡糖(alginate oligosaccharide,AOS)是褐藻胶的降解产物,由于其分子量低、水溶性高、安全无毒等特点,近年来受到广泛关注.AOS独特的...