Synthesis and Biological Study of 4-Aminopyridine-Peptide Derivatives Designed for the Treatment of Neurodegenerative Disorders.

Background: Alzheimer's disease (AD) and Multiple sclerosis (MS) lead to neurodegenerative processes negatively affecting millions of people worldwide. Their treatment is still difficult and practically incomplete. One of the most commonly used drugs against these neurodegenerative diseases is 4-aminopyridine.

Neuroprotective effect of newly synthesized 4-aminopyridine derivatives on cuprizone-induced demyelination in mice-a behavioral and immunohistochemical study.

The aim of this study was to assess the effect of newly synthesized derivatives of 4-aminopyridine (4-AP) on cuprizone-induced model of brain demyelination in mice. 4-AP is already approved for the treatment of walking difficulties in patients with multiple sclerosis. The model of demyelination was carried out by the administration of cuprizone to the drinking water of the experimental mice.

Effect of Original Peptide Derivatives of Galantamine on Passive Avoidance in Mice.

The effect of original peptide derivatives of galantamine on scopolamine-induced memory impairment in mice was assessed using the passive avoidance test over 12 days. It was found that some galantamine derivatives administered in a dose of /LD improved the memory in experimental mice, especially on days 5-12 of the experiment.

In vivo toxicity assessment of Clinopodium vulgare L. water extract characterized by UHPLC-HRMS.

Clinopodium vulgare L. (Lamiaceae) was used in the traditional Bulgarian medicine for treatment of wounds, diabetes and gastric ulcers. In this study we aimed at safety assessment of C.

Bone protective effects of purified extract from Ruscus aculeatus on ovariectomy-induced osteoporosis in rats.

Ruscus aculeatus is a source of steroidal saponins that could mimic sex hormones and could help alleviate the risk of fracture in osteoporotic patients. The aim of the present study was to evaluate the in vitro effects of an extract from R. aculeatus (ERA) on the proliferation of human osteoblast-like SaOS-2 cell line and to investigate the effects of the ERA administered orally for 10 weeks at three doses (50, 100 and 200 mg/kg) on the bone structure of rats with estrogen deficiency induced by bilateral ovariectomy.

Synthesis of New Galanthamine-Peptide Derivatives Designed for Prevention and Treatment of Alzheimer's Disease.

Background: Although no effective treatment for the Alzheimer's disease currently exist, some drugs acting as Acetylcholinesterase inhibitors, like galanthamine have positively affected such patients. β- and/or γ-secretase inhibitors are another type of potential drugs. Here we report synthesis of new peptide-galanthamine derivatives, with expected inhibitory activity against both Acetylcholinesterase and β-secretase.

Delineation of proapoptotic signaling of anthracene-shelled ML metallacapsules and their synergistic activity with curcumin in cisplatin-sensitive and resistant tumor cell lines.

Since the introduction of cisplatin into clinical practice a few decades ago, the topic of metal-based drugs has expanded significantly. Recent examples emphasize on metallosupramolecules as an emerging class of compounds with diverse properties. They can trigger unique cellular events in malignant cells or serve as molecular hosts for various biologically active compounds, including anticancer agents.

Hepatoprotective and antioxidant potential of Asphodeline lutea (L.) Rchb. roots extract in experimental models in vitro/in vivo.

The aim of this study was to investigate the effect of Asphodeline lutea (L.) Rchb. dry root extract (ALE) administered alone and against carbon tetrachloride (CCl)-induced liver injury in vitro/in vivo.

Synthesis of New Peptide Derivatives of Galanthamine Designed for Prevention and Treatment of Alzheimer's Disease.

New derivatives of galanthamine containing peptide fragments with β-secretase inhibitor activity were synthesized. In position 6 of the galanthamine new shortened analogues of β-secretase inhibitor OM 99-2 (Boc-Val-Asn-Leu-Ala-OH and Boc-Val-Asn-Leu-Ala-Val-OH) were included. The new derivatives of the galanthamine in position 11 including Boc and norgalanthamine in P3 or P4 positions, Val in P2' position and benzylamin in P3'-position were also synthesized.

Pharmacological investigations of new galantamine peptide esters.

Galantamine hydrobromide (GAL) is a reversible acetylcholinesterase inhibitor, with properties to increase the concentration of acetylcholine in several brain structures. The aim of this study is to determine the effect of new galantamine peptide esters: 3,4-dichlorophenyl-alanil-leucil-glycine-galantamine (GAL-LEU) and 3,4-dichlorophenyl-alanil-valil-glycine-galantamine (GAL-VAL), on locomotor activity in mice and cognitive processes in experimental model of learning and memory in rats. The results showed that per oral administration of GAL-LEU in a dose of 3 mg per kg improved the cognitive processes by increasing the conditional avoidances and learning ability after the 5th day of application and preserved the memory at the 12th day of the study.

Assessment of surgical sutures POLYMED(®) by intracutaneous irritation test in rabbits.

The aim of the present study was to evaluate local irritant effects to rabbit skin following a single application of test samples of non-sterile polyamide non-absorbable surgical sutures POLYMED(®). The polar and nonpolar extracts were prepared by using saline solution and olive oil, respectively, after sinking the materials tested (2.0 g) in 10 ml of the corresponding liquid.

Pharmacokinetics of cytisine after single intravenous and oral administration in rabbits.

The aim of this study is to develop a sensitive HPLC method for the quantitative determination of cytisine in serum and to characterize the pharmacokinetic behaviour of cytisine after oral and intravenous administration in rabbits. The pharmacokinetic behaviour of cytisine is studied in male and female New Zealand rabbits after oral and intravenous administration. Cytisine is administered orally (dose of 5 mg/kg b.

[Drugs in pregnancy].

The use of drugs in pregnancy is being discussed. The influence of different factors, both physiological and drug related (physicochemical characteristics, dose, duration of pharmacotherapy) on the processes of absorption, distribution, protein binding, metabolism and excretion are reviewed. The up-to-date classification of the drugs in relation to their effects on the fetus is presented.

Synthesis and brain antihypoxic activity of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid.

The synthesis of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid was studied. The structures of synthesized compounds were proved by micro-analyses, IR- and 1H NMR data. Values of acute p.

Synthesis, acute toxicity, and analgesic activity of new derivatives of pyrrole.

Ten pyrrole derivatives (including six new compounds) were synthesized and evaluated as potential platform for analgesic agents' development. Acute intraperitoneal toxicity and analgesic activity studies (acetic acid writhing test) were performed on mice with acetylsalicylic acid used as a reference substance. Products 3c, 3d, 3e, and 3h exhibited a dose-dependent activity demonstrating 1.

Synthesis and anticoagulant activities of substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins.

Different substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins are the final products when 4-hydroxycoumarin and aromatic aldehydes containing hydroxyl group in o-, m,- or p-position condense in boiling ethanol. We synthesized 14 compounds. Three of them are described for the first time.

Synthesis, structure, toxicological and pharmacological investigations of 4-hydroxycoumarin derivatives.

Twenty 4-hydroxycoumarin derivatives were synthesized. Five of them are described for the first time. The X-ray crystal structure analysis of 3,3'-(2,3,4-trimethoxyphenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (7) and 3,3'-(3,5-dimethoxy-4-hydroxyphenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (9) confirmed the structure of these compounds.

Phytochemical analysis of ethyl acetate extract from Astragalus corniculatus Bieb. and brain antihypoxic activity.

Dry ethyl acetate extract containing flavonoids was obtained from above-ground parts of Astragalus corniculatus Bieb. Seven flavonoids were isolated and identified as rutin, hyperoside, isoquercitrin, narcissin, quercetin, kaempferol and isorhamnetin for the first time. The extract was found to be practically non-toxic (acute oral toxicity > 5 g kg(-1) in mice).

The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats.

The actions of the synthetic heptapeptide preparation Selank on learning and memory processes in rats with initially low levels of learning ability were compared with those in normal rats, using a method based on acquisition of a conditioned active avoidance reflex, with repeated administration of peptide 15 min before the start of training sessions for four days. The effects of Selank (300 microg/kg) were compared with the effects of the nootrope piracetam (400 mg/kg). These experiments showed that Selank significantly activated the learning process in rats with initially poor learning ability, with effects apparent after first dose on training day 1.

Synthesis and pharmacological investigations of some 4-hydroxycoumarin derivatives.

The synthesis of ten coumarin derivatives of 4-hydroxycoumarin and various unsaturated ketones and aldehydes is described. The structures of the synthesized compounds were confirmed by IR, (1)H-NMR, and mass-spectral data. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration.

[Optimizing action of synthetic peptide Selank on active avoidance conditioning test in rats].

The action of a synthetic peptide Selank on learning and memory in active avoidance conditioning test was studied in rats with initially low learning ability and normal animals. The peptide was administered repeatedly 15 min prior the training session (4 days). The effect of Selank (300 micrograms/kg) was compared to that of Pyracetam (400 mg/kg).

Polyamine uptake is necessary for a normal biochemical maturation of astrocytes in culture.

In this study we have explored the importance of polyamine uptake in the proliferation and biochemical maturation of cerebellar astroyctes in culture. The uptake of polyamines paralleled astrocyte proliferation measured as [3H]thymidine incorporation into the DNA. Inhibition of polyamine uptake did not alter the developmental profile of thymidine incorporation, perhaps due to a compensatory increase in ornithine decarboxylase activity but was able to reduce glutamine synthetase (GS) activity, an enzymatic marker for astrocyte biochemical maturation, from 9 days in vitro.

Copper(II) complexes of the beta-blocker pindolol: properties, structure, biological activity.

The complex formation between copper(II) and the antihypertensive drug pindolol (HPin) was studied both in aqueous and methanolic media. Two complexes are formed at different metal-to-ligand molar ratios. The mononuclear complex Cu(Pin)2(HPin)2 contains two ligands in an anionic bidentate form and two--in a neutral form bound monodentately.

New metal complexes of 4-methyl-7-hydroxycoumarin sodium salt and their pharmacological activity.

Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds.

Synthesis, brain antihypoxic activity and cell neuroprotection of 1-substituted-3,7-dimethylxanthines.

Five newly synthesised original compounds were investigated for acute toxicity, influence on hexobarbital sleeping time, effect on the locomotor activity, and brain antihypoxic activity. Two of the compounds were tested in a model of glutamate induced neurotoxicity in the brain cell culture using a cell viability test. Our studies indicate that compounds 2a-c and 4 prolonged the survival time of mice in the model of anoxic hypoxia.