Coordination complexes of 3,4-dihydroxyphenylpropionic acid (dihydrocaffeic acid) with copper(II), nickel(II), cobalt(II) and iron(III)

Summary The preparation of complexes of 3,4-dihydroxyphenylpropoionic acid (hydrocaffeic acid): K₂[Cu₂(hydcafH)₂-Cl₂]·2KCl·2MeOH, K₂[Co(hydcafH)₂]·2KCl, K₂[Ni₂(hydcafH)₂Cl₂]·2KCl·2MeOH and Fe₂ (hydcafH)₂Cl₂·2KCl·2H₂O was achieved. Spectroscopic and magnetic studies are commensurate with tetrahedral structures for the prepared complexes in which the catechol-like coordination is present.     

Thiazole Ring—A Biologically Active Scaffold

Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years.     

Synthesis and Neurotropic Activity of New Heterocyclic Systems: Pyridofuro[3,2-d]pyrrolo[1,2-a]pyrimidines,Pyridofuro[3,2-d]pyrido[1,2-a]pyrimidines and Pyridofuro[3′,2′:4,5]pyrimido[1,2-a]azepines

Background: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore. Benzodiazepines enhance GABA-ergic transmission and this has led to a study of the role of GABA in anxiety. The search for anxiolytics and anticonvulsive agents has involved glutamate-ergic, 5HT-ergic substances and neuropeptides. However, each of these well-known anxiolytics, anticonvulsants and cognition enhancers (nootropics) has repeatedly been reported to have many adverse side effects, therefore there is an urgent need to search for new drugs able to restore damaged cognitive functions without causing significant adverse reactions. Objective: Considering the relevance of epilepsy diffusion in the world, we have addressed our attention to the discovery of new drugs in this field Thus our aim is the synthesis and study of new compounds with antiepileptic (anticonvulsant) and not only, activity. Methods: For the synthesis of compounds classical organic methods were used and developed. For the evaluation of biological activity some anticonvulsant and psychotropic methods were used. Results: As a result of multistep reactions 26 new, five-membered heterocyclic systems were obtained. PASS prediction of anticonvulsant activity was performed for the whole set of the designed molecules and probability to be active Pa values were ranging from 0.275 to 0.43. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures, anti-thiosemicarbazides effect as well as some psychotropic effect. The biological assays evidenced that some of the studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of compounds is low and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity it was found that the selected compounds have an activating behavior and anxiolytic effects on the models of “open field” and “elevated plus maze” (EPM). The data obtained indicate the anxiolytic (anti-anxiety) activity of the derivatives of pyrimidines, especially pronounced in compounds 6n, 6b, and 7c. The studied compounds increase the latent time of first immobilization on the model of “forced swimming” (FST) and exhibit some antidepressant effect similarly to diazepam. Docking studies revealed that compound 6k bound tightly in the active site of GABA_A receptor with a value of the scoring function that estimates free energy of binding (ΔG) at −7.95 kcal/mol, while compound 6n showed the best docking score and seems to be dual inhibitor of SERT transporter as well as 5-HT_1A receptor. Conclusions: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects, at the same time exhibit some antidepressant effect.     

Internal transitions of negatively charged magnetoexcitons and many body effects in a two-dimensional electron gas

Internal transitions of quasi-two-dimensional, negatively charged magnetoexcitons ( X-) and their evolution with excess electron density have been studied in GaAs/AlGaAs quantum wells. In the dilute electron limit, due to magnetic translational invariance, the optically detected resonance spectra are dominated by bound-to-continuum bands in contrast to the negatively charged donor system D-, which exhibits strictly bound-to-bound transitions. With increasing excess electron density Landau-level filling factors nu<2 the X--like transitions are blueshifted; they are absent for nu>2. The blueshifted transitions are explained in terms of a new type of collective excitation---magnetoplasmons bound to a mobile valence band hole.     

Optically detected resonance spectroscopy of interface fluctuation quantum dots

We have performed optically detected resonance (ODR) spectroscopy on modulation-doped GaAs/AlGaAs quantum wells of different widths in which lateral fluctuations of the well width were purposely introduced by growth interruption at the interfaces. These monolayer fluctuations form quantum dots for which confinement and Coulomb correlation energies are comparable. By monitoring resonant changes of the dot ensemble photoluminescence induced by far-infrared (FIR) radiation in a magnetic field, we have observed cyclotron resonance (CR) of free electrons in the widest wells, as well as internal transitions of mobile and localized charged excitons. The latter, which are forbidden by magnetic translational invariance, have previously not been observed. For the narrower wells the effects of non-parabolicity and carrier localization on the CR and CR-like transitions have to be included for a proper interpretation of the measurements.     

Determination of growth hormone releasing peptides (GHRP) and their major metabolites in human urine for doping controls by means of liquid chromatography mass spectrometry

A family of small peptides has reached the focus of doping controls representing a comparably new strategy for cheating sportsmen. These growth hormone releasing peptides (GHRP) are orally active and induce an increased production of endogenous growth hormone (GH). While the established test for exogenous GH fails, the misuse of these prohibited substances remains unrecognized. The present study provides data for the efficient extraction of a variety of known drug candidates (GHRP-1, GHRP-2, GHRP-4, GHRP-5, GHRP-6, alexamorelin, ipamorelin, and hexarelin) from human urine with subsequent mass spectrometric detection after liquid chromatographic separation. The used method potentially enables the retrospective evaluation of the acquired data for unknown metabolites by means of a non-targeted approach with high-resolution/high-accuracy full-scan mass spectrometry with additional higher collision energy dissociation experiments. This is of great importance due to the currently unknown metabolism of most of the targets and, thus, the method is focused on the intact peptidic drugs. Only the already characterised major metabolite of GHRP-2 (d-Ala-d-2-naphthylAla-l-Ala, as well as its stable isotope-labelled analogue) was synthesised and implemented in the detection assay. Method validation for qualitative purpose was performed with respect to specificity, precision (<20%), intermediate precision (<20%), recovery (47–95%), limit of detection (0.2–1 ng/mL), linearity, ion suppression and stability. Two stable isotope-labelled internal standards were used (deuterium-labelled GHRP-4 and GHRP-2 metabolite). The proof-of-principle was obtained by the analysis of excretion study urine samples obtained from a single oral administration of 10 mg of GHRP-2. Here, the known metabolite was detectable over 20 h after administration while the intact drug was not observed.