RGD mimetics containing a central hydantoin scaffold: alpkha(v)beta3 vs alpha(IIb)beta3 selectivity requirements

The synthesis of a series of RGD mimetic alpha(v)beta3 antagonists containing a hydantoin scaffold is shown. The results demonstrate some of the structural requirements for the design of selective alpha(v)beta3 antagonists (vs alpha(IIb)beta3) in terms of the Arg-mimetic, the distance between N- and C-terminus and the lipophilic side chain.     

Discovery of 12-(S)-hydroxy-5,8,10,14-icosatetraenoic acid [12-(S)-HETE] in the tropical red alga Platysiphonia miniata

The potent mammalian immunohormone, 12-(S)-hydroxy-5,8,10,14-icosatetraenoic acid (12-(S)-HETE), is a 12-lipoxygenase metabolite of arachidonic acid that is widely distributed in animal tissues. In humans, it is produced and secreted by platelet cells and elicits both chemotactic and degranulatory responses in target neutrophils. As widely as 12-lipoxygenase activity and one of its major products, 12-(S)-HETE, have been found in animal tissues, it has never been found in plants. Herein, we report the first isolation of the 12-lipoxygenase product, 12-(S)-HETE, from a plant, the tropical marine alga Platysiphonia miniata (C. Agardh) B?rgesen.     

Comparison of old and new wheat cultivars in Iran by measuring germination related traits,osmotic tolerance and ISSR diversity

A primary concern of modern plant breeding is that genetic diversity has decreased during the past century. This study set out to explore changes in genetic variation during 84 years of breeding by investigating the germination-related traits, inter-simple sequence repeat (ISSR) fingerprinting and osmotic stress tolerance of 30 Iranian wheat (Triticum aestivum L.) cultivars. Seeds were planted under control and osmotic stress (?2, ?4 and ?6 bar) in three replications. The ISSR experiment was carried out using 32 different primers. Genotypes were divided into two groups (old and new) each containing 15 members. The results of ANOVA showed that highly significant differences existed among genotypes and among growth conditions. The results showed that during breeding in some traits such as coleoptile length and seedling vigor index, a significant decrease has been occurred. New cultivars had a mean coleoptile length of 33 mm, shorter than that of old cultivars (42 mm) under osmotic stress of ?6 bar. Genetic variance of root length, shoot length and seedling vigor index for old cultivars were 1.59, 1.93 and 45,763, respectively, significantly higher than those for new cultivars (0.55, 1.08 and 27,996, respectively). This difference was also verified by ISSR results as the polymorphism information content was 0.28 in old cultivars, higher than that of new cultivars (0.26). These results prove this claim that during breeding, genetic diversity has decreased for many germination-related traits and breeders are better to pay more attention to genetic diversity.     

Development and validation of a stability-indicating high performance liquid chromatographic (HPLC) assay for biperiden in bulk form and pharmaceutical dosage forms

Current compendial (USP) methods of assay for the analysis of biperiden in bulk form and pharmaceutical dosage forms involve the use of titrimetric and spectrophotometric procedures, respectively. These are non-selective and non-stability-indicating techniques. In this work, a stability-indicating high performance liquid chromatographic assay procedure has been developed and validated for biperiden. The liquid chromatographic separation was achieved isocratically on a symmetry C8 column (150 mm x 3.9 mm i.d., 5 microm particle size) using a mobile phase containing methanol-buffer (50:50, v/v, pH 2.50) at a flow rate of 1 ml/min and UV detection at 205 nm. The buffer was composed of sodium dihydrogen phosphate (50 mM) and 1-heptanesulfonic acid sodium salt (5 mM). The method was linear over the concentration range of 0.5-25 microg/ml (r=0.9998) with a limit of detection and quantitation 0.03 and 0.1 microg/ml, respectively. The method has the requisite accuracy, selectivity, sensitivity and precision to assay biperiden in bulk form and pharmaceutical dosage forms. Degradation products resulting from the stress studies did not interfere with the detection of biperiden and the assay is thus stability-indicating.     

Hormetic effects of curcumin: What is the evidence?

Curcumin (diferuloylmethane), a component of the yellow powder prepared from the roots of Curcuma longa or Zingiberaceae (known as turmeric) is not only widely used to color and flavor food but also used as a pharmaceutical agent. Curcumin demonstrates anti-inflammatory, anticarcinogenic, antiaging, and antioxidant activity, as well as efficacy in wound healing. Notably, curcumin is a hormetic agent (hormetin), as it is stimulatory at low doses and inhibitory at high doses. Hormesis by curcumin could be also a particular function at low doses (i.e., antioxidant behavior) and another function at high dose (i.e., induction of autophagy and cell death). Recent findings suggest that curcumin exhibits biphasic dose–responses on cells, with low doses having stronger effects than high doses; examples being activation of the mitogen-activated protein kinase signaling pathway or antioxidant activity. This indicates that many effects induced by curcumin are dependent on dose and some effects might be greater at lower doses, indicative of a hormetic response. Despite the consistent occurrence of hormetic responses of curcumin in a wide range of biomedical models, epidemiological and clinical trials are needed to assess the nature of curcumin’s dose–response in humans. Fortunately, more than one hundred clinical trials with curcumin and curcumin derivatives are ongoing. In this review, we provide the first comprehensive analysis supportive of the hormetic behavior of curcumin and curcumin derivatives.     

DNA-PHONA-PNA Chimeric Molecules: Contributions to Binding Against Complementary DNA

Abstract

The synthesis of a DNA-PHONA-PNA chimeric molecule using the Mmt protection strategy is described. The chimeric oligomer shows duplex binding properties that are comparable to PNA. Obviously, PHONA building blocks can be incorporated into PNAs without distortion of the PNA structure

     

Novel 3-chlorooxazolidin-2-ones as antimicrobial agents

Antimicrobial resistance against many known therapeutics is on the rise. We examined derivatives of 3-chlorooxazolidin-2-one 1a (X = H) as antibacterial and antifungal agents. The key findings were that the activity and apparent in vitro cytotoxicity could be controlled by the substitution of charged solubilizers at the 4- and 5- positions. These changes both significantly increase the antifungal potency and decrease cytotoxicity. Particularly effective were trialkylammonium groups which led to 400- to 600-fold increases in the antifungal therapeutic index when compared to their unsubstituted counterparts.