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Among the various drug discovery methods, a very promising modern approach consists in designing multi-target-directed ligands (MTDLs). This methodology has been specifically developed for treatment of disorders with complex pathological mechanisms. One such disorder is Alzheimer's disease (AD), currently the most common multifactorial neurodegenerative(More)
Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer's disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and(More)
We examined the influence of caffeine on honeybee lifespan, Nosema resistance, key enzyme activities, metabolic compound concentrations, and total DNA methylation levels. Caffeine slowed age-related metabolic tendencies. Bees that consumed caffeine lived longer and were not infested with Nosema spp. Caffeine-treated workers had higher protein(More)
In this paper a series of new 1,3,4-thiadiazole derivatives has been designed, synthesized and evaluated as the acetyl- and butyrylcholinesterase inhibitors. Some analogues showed promising inhibition of both enzymes in vitro in the nM range. Generally, inhibitory potency of compounds was stronger against AChE than BuChE, and one of them was 1154-fold more(More)
β-amyloid aggregation and formation of senile plaques is one of the hallmarks of Alzheimer's disease (AD). It leads to degeneration of neurons and decline of cognitive functions. The most aggregative and toxic form of β-amyloid is Aβ1-42 but in experiments, the shorter forms able to form aggregates are also used. The early stages of amyloid formation are of(More)
A series of derivatives of dihydrofuran-2(3H)-one (γ-butyrolactone, GBL) was synthesized and tested for anticonvulsant, neurotoxic and analgesic activity. In the anticonvulsant screening 10 lactones were effective in the maximal electroshock test (MES) at the highest doses (300 and 100 mg/kg, 0.5 h, ip, mice). Statistical analysis showed correlation between(More)
Based on the fact that the thymidine phosphorylase inhibitors are considered potential anti-tumor agents, a range of novel oxadiazole derivatives 3a-3u was designed and synthesized by a simple and facile synthetic route. The biological assay revealed that majority of compounds displayed modest inhibitory activity against thymidine phosphorylase at low(More)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system (CNS) which is the most common cause of dementia in the elderly. It is characterized by the deficits in the cholinergic system and presence of characteristic hallmarks: neurofibrillary tangles and amyloid plaques. Since the cholinergic system plays an(More)
The lipophilicity of a series of anticancer propargylthioquinoline derivatives has been investigated using chromatographic and computational methods. The parameters of relative lipophilicity (R(MO) and logk0) of the tested compounds were determined experimentally both by reversed-phase thin layer (RP-TLC), and high-performance liquid chromatographic methods(More)
An association between α(1)-adrenoceptor affinities, hERG K(+)-antagonistic properties and antiarrhythmic activities for a series of phenylpiperazine derivatives of hydantoin (2a-21a) was investigated. New compounds were synthesized and tested for their affinity for α(1)-adrenoceptors in radioligand binding assay using [(3)H]-prazosin as a selective(More)