Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

Pyrrole, pyrrolidine, pyridine, piperidine and tropane alkaloids

https://www.gastrojournal.org/article/S0016-5085(13)00292-8/pdf

Consumption of Fermented Milk Product with Probiotic Modulates Brain Activity

Alkaloids mimicking the structures of monosaccharides are now believed to be widespread in plants and microorganisms, and these sugar mimics inhibit glycosidases because of a structural resemblance to the sugar moiety of the natural substrate. Naturally occurring sugar mimics with a nitrogen in the ring are classified into five structural classes: polyhydroxylated piperidines, pyrrolidines, indolizidines, pyrrolizidines and nortropanes. Glycosidases are involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins and the lysosomal catabolism of glycoconjugates. The realization that alkaloidal sugar mimics might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes has led to increasing interest and demand for these compounds. Most of these effects can be shown to result from the direct or indirect inhibition of glycosidases. The glycosphingolipid (GSL) storage diseases are relatively rare hereditary disorders that are severe in nature and frequently fatal. Possible strategies for the treatment of these lysosomal storage diseases include enzyme replacement therapy, gene therapy and substrate deprivation. Recently, quite a new therapy for lysosomal storage diseases has been reported, namely a ‘chemical chaperone therapy’ for Fabry disease. In this report, the structural basis for the specificity of inhibition of alkaloidal sugar mimics and their current and potential application to biomedical problems will be reviewed.

Sugar-mimic glycosidase inhibitors: natural occurrence, biological activity and prospects for therapeutic application

https://www.cell.com/trends/cognitive-sciences/pdf/S1364-6613(12)00027-7.pdf

Ventromedial prefrontal-subcortical systems and the generation of affective meaning

Polyhydroxylated alkaloids -- natural occurrence and therapeutic applications.

Matricaria chamomilla L., known as “chamomile”, has been used as an herbal tea or supplementary food all over the world. We investigated the effects of chamomile hot water extract and its major components on the prevention of hyperglycemia and the protection or improvement of diabetic complications in diabetes mellitus. Hot water extract, esculetin (3) and quercetin (7) have been found to show moderate inhibition of sucrase with IC50 values of 0.9 mg/mL and 72 and 71 μM, respectively. In a sucrose-loading test, the administration of esculetin (50 mg/kg body weight) fully suppressed hyperglycemia after 15 and 30 min, but the extract (500 mg/kg body weight) and quercetin (50 mg/kg body weight) were less effective. On the other hand, a long-term feed test (21 days) using a streptozotocin-induced rat diabetes model revealed that the same doses of extract and quercetin showed significant suppression of blood glucose levels. It was also found that these samples increased the liver glycogen levels. Moreover, cha...

/pdf/protective-effects-of-dietary-chamomile-tea-on-diabetic-5bp6ufu180.pdf

Protective Effects of Dietary Chamomile Tea on Diabetic Complications

Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation of the pain matrix in the brain. However it is not clear whether the placebo response is reproducible within individuals and what role personality traits might play in predicting it. We induced placebo analgesia by conditioning subjects to expect pain reduction following a sham-treatment in the guise of a local anaesthetic cream applied to one arm. Pain ratings were assessed before, during and after treatment. The procedure was repeated in a second session to assess the degree of reproducibility of the response. A high degree of correlation was found between the two sessions for the sham-treatment group (R(2) = 0.55; p < 0.001). Personality questionnaires were given during both experimental sessions to assess key traits such as optimism and state and trait anxiety. A regression model was used to statistically define a placebo responder in terms of personality scores. High dispositional optimism and low state anxiety were found to be significant predictors of placebo response. We suggest that repeated placebo responders are high in dispositional optimism and having a placebo response in the first session causes a drop in state anxiety at the beginning of the repeat session.

Reproducibility of placebo analgesia: Effect of dispositional optimism

The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. In the control session participants were explicitly told that the treatment was inactive. The sham treatment group reported a significant reduction in pain rating (p=0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia.

/pdf/placebo-conditioning-and-placebo-analgesia-modulate-a-common-3w69k0x8wj.pdf

Placebo conditioning and placebo analgesia modulate a common brain network during pain anticipation and perception

There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain, and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological, and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.

https://www.jneurosci.org/content/jneuro/31/45/16117.full.pdf

Alison A. Watson

Papers

Polyhydroxylated alkaloids -- natural occurrence and therapeutic applications.

Protective Effects of Dietary Chamomile Tea on Diabetic Complications

Reproducibility of placebo analgesia: Effect of dispositional optimism

Placebo conditioning and placebo analgesia modulate a common brain network during pain anticipation and perception

The Placebo Effect: Advances from Different Methodological Approaches