A closer look at molecular mechanisms underlying inhibition of -adenosyl-L-homocysteine hydrolase by transition metal cations.

We report biochemical and structural studies on inhibiting bacterial -adenosyl-L-homocysteine hydrolase by transition metal cations. Our results revealed diverse molecular mechanisms of enzyme inactivation. Depending on the cation, the mechanism is based on arresting the enzyme in its closed, inactive conformation, disulfide bond formation within the active site or oxidation of the intermediate form of a cofactor.

Biochemical and structural insights into an unusual, alkali-metal-independent S-adenosyl-L-homocysteine hydrolase from Synechocystis sp. PCC 6803.

The mesophilic cyanobacterium Synechocystis sp. PCC 6803 encodes an S-adenosyl-L-homocysteine hydrolase (SAHase) of archaeal origin in its genome. SAHases are essential enzymes involved in the regulation of cellular S-adenosyl-L-methionine (SAM)-dependent methylation reactions.

Synthesis and Structural Characterization of Pyridine-2,6-dicarboxamide and Furan-2,5-dicarboxamide Derivatives.

Derivatives based on pyridine-2-6- and furan-2,5-dicarboxamide scaffolds reveal numerous chemical properties and biological activities. This fact makes them an exciting research topic in supramolecular and coordination chemistry and in discovering new pharmacologically-active compounds. This work aimed to obtain a series of symmetrical pyridine-2-6- and furan-2,5-dicarboxamides through a condensation reaction of the appropriate acyl chlorides and aromatic amides.

A new look at two polymorphic crystal structures of dibenzoylmethane: relationship between the crystal packing and the hydrogen atom position revealed by quantum chemistry and quantum crystallography methods.

Chalcones, including dibenzoylmethane, are an important subgroup of natural polyphenolic compounds that exhibit a wide spectrum of pharmacological and industrial applications. Dibenzoylmethane was isolated from Hottonia palustris L. (Primulaceae).

Potential antidepressant-like properties of the TC G-1008, a GPR39 (zinc receptor) agonist.

Some forms of depression appear to be more related to the glutamatergic system. G-coupled protein receptor 39 (GPR39) is the metabotropic zinc receptor, which may be involved in the pathophysiology of depression and in the antidepressant response. Its deficiency abolishes the antidepressant response, which means that GPR39 is required to obtain a therapeutic effect in depression.

The anxiolytic-like activity of a novel N-cycloalkyl-N-benzoylpiperazine derivative.

Background: Anxiety-related disorders are among the most common mental illnesses in the world for which benzodiazepines, buspirone and antidepressant drugs remain the first-line treatment. These drugs have good efficacy but they have numerous disadvantages, such as drug abuse potential, delayed onset of action or tolerance. A literature review reveals that a variety of piperazine derivatives may exhibit interesting pharmacological properties, including anxiolytic-like, antidepressant, nootropic and antinociceptive activities demonstrated in animal models, as well as an antioxidant capacity shown in some in vitro tests.

Investigation of the GPR39 zinc receptor following inhibition of monoaminergic neurotransmission and potentialization of glutamatergic neurotransmission.

Zinc can regulate neural function in the brain via the GPR39 receptor. In the present study we investigated whether inhibition of serotonin, noradrenaline and dopamine synthesis and potentialization of glutamate, via administration of p-chlorophenylalanine (pCPA), α-methyl-p-tyrosine (αMT) and N-methyl-D-aspartatic acid (NMDA), respectively, would cause changes in GPR39 levels. Western blot analysis showed GPR39 up-regulation following 3-day administration of αMT and NMDA in the frontal cortex, and GPR39 down-regulation following 10-day administration of pCPA, αMT, and NMDA in the hippocampus of CD-1 mice.

Study of antidepressant drugs in GPR39 (zinc receptor⁻/⁻) knockout mice, showing no effect of conventional antidepressants, but effectiveness of NMDA antagonists.

The monoamine-based antidepressants that are currently used generate many side effects, and more than 30% of depressed patients do not respond to this therapy. Glutamate-based antidepressants seem to play an important role in therapy for depression, but there is still an extensive search for safe drugs. An antagonist of the glutamatergic NMDA receptor - namely, zinc - plays a part in maintaining homeostasis between glutamate and GABA via the GPR39 receptor, which has been found to be involved in the pathophysiology of depression.

Essential elements in depression and anxiety. Part II.

In this paper we continue to discuss the involvement of essential elements in depression and anxiety, and the possible mechanisms that link elements to the neurobiology underlying depression/anxiety. The present paper is focused on copper, selenium, manganese, iodine and vanadium. Different aspects of relationship between elements and depression or anxiety are reviewed, e.

An overview of the pharmacological properties and potential applications of natural monoterpenes.

Monoterpenes, the major components of essential oils, belong to the group of isoprenoids containing ten carbon atoms. Being widely distributed in the plant kingdom they are extensively used in cuisine and human health care products. Studies have shown that both natural monoterpenes and their synthetic derivatives are endowed with various pharmacological properties including antifungal, antibacterial, antioxidant, anticancer, antiarrhythmic, anti-aggregating, local anesthetic, antinociceptive, anti-inflammatory, antihistaminic and anti-spasmodic activities.

Chronic treatment with zinc hydroaspartate induces anti-inflammatory and anti-ulcerogenic activity in rats.

Background: The previous study indicated the enhancement of the anti-inflammatory effect of ketoprofen by acute and sub chronic administration of zinc hydroaspartate.

Methods: The present study examined anti-inflammatory, anti-ulcerogenic and analgesic activity induced by chronic (14 days) administration of ZHA (30 mg/kg, po), with a combination of a single administration of ketoprofen, in rats. Moreover, the zinc concentration in serum and stomach mucosa was also determined.

Influence of zinc hydroaspartate on the anti-inflammatory and gastric activity of ketoprofen in rats.

Background: The study's aim was to evaluate the anti-inflammatory effect and influence on gastric mucosa after the combined administration of ketoprofen and zinc hydroaspartate (ZHA, 60 mg/kg).

Methods: Antiedematous activity was determined according toWinter et al., analgesic activity according to the Randall and Selitto test, the influence on gastric mucosa in accordance to Komatsu.