Abietic acid, a naturally occurring fir resin compound, that exhibits anti-inflammatory and wound-healing properties, was formulated into biocompatible emulgels based on stable microemulsions with the addition of a carbamate-containing surfactant and Carbopol^® 940 gel. Various microemulsion and emulgel formulations were tested for antioxidant and wound-healing properties. The chemiluminescence method has shown that all compositions containing abietic acid have a high antioxidant activity. Using Strat-M^® skin-modelling membrane, it was found out that emulgels significantly prolong the release of abietic acid. On Wistar rats, it was shown that microemulsions and emulgels containing 0.5% wt. of abietic acid promote the rapid healing of an incised wound and twofold tissue reinforcement compared to the untreated group, as documented by tensiometric wound suture-rupture assay. The high healing-efficiency is associated with a combination of antibacterial activity of the formulation components and the anti-inflammatory action of abietic acid.

In this study, novel derivatives based on 6-methyluracil and condensed uracil were synthesized, namely, 2,4-quinazoline-2,4-dione with ω-(ortho-nitrilebenzylethylamino) alkyl chains at the N atoms of the pyrimidine ring. In this series of synthesized compounds, the polymethylene chains were varied from having tetra- to hexamethylene chains, and secondary NH, tertiary ethylamino, and quaternary ammonium groups were introduced into the chains. The molecular modeling of the compounds indicated that they could function as dual binding site acetylcholinesterase inhibitors, binding to both the peripheral anionic site and active site. The data from in vitro experiments show that the most active compounds exhibit affinity toward acetylcholinesterase within a nanomolar range, with selectivity for acetylcholinesterase over butyrylcholinesterase reaching four orders of magnitude. In vivo biological assays demonstrated the potency of these compounds in the treatment of memory impairment using an animal model of Alzheimer disease.

Terminal Schwann cells (TSCs) are capable of regulating acetylcholine (ACh) release at the neuromuscular junction (NMJ). We have identified GABA as a gliotransmitter at mouse NMJs. When ACh activates α7 nicotinic ACh receptor (nAChRs) on TSCs, GABA is released and activates GABA_B receptors on the nerve terminal that subsequently reduce ACh release. Indeed, specific deletion of the α7 nAChR in TSCs or inhibition of the metabotropic GABA_B receptor prevents the reduction in the quantal content of the end‐plate potential induced by cholinesterase inhibitors. The α7/GABA_B receptor‐mediated pathway is activated when ACh that escapes from collagen Q (ColQ) anchored AChE in the synaptic cleft and from PRiMA‐anchored butyrylcholinesterase on the TSC activates α7 nAChRs on the TSC. Consequently, prolonged tetanic stimulation of isolated muscle activates the α7/GABA_B receptor pathway, which reduces post‐tetanic ACh release. When AChE levels are low in neonatal mice, the α7/GABA_B receptor‐mediated pathway decreases ACh release and reduces ex vivo muscle fatigue. For ColQ‐deficient mice where AChE is not clustered, the decrease in AСh release following activation of this pathway contributes to mouse fatigue in vivo. image Key points: Acetylcholine (ACh) released from the nerve terminal at the neuromuscular junction (NMJ) can activate α7 nicotinic ACh receptor (nAChR) on terminal Schwann cells, releasing gamma‐aminobutyric acid (GABA) that activates metabotropic GABA_B receptors on the nerve terminal which then reduces further ACh release from the nerve. At the mature NMJ, before reaching α7 nAChRs on terminal Schwann cells ACh is normally hydrolyzed by AChE clustered in the synaptic cleft and by BChE anchored to the TSC. ACh can activate the α7/GABAB receptor‐mediated pathway and depress subsequent ACh release when AChE at the NMJ is low, either during development or in congenital myasthenic syndrome. In the latter case, this pathway contributes to muscle fatigue.

Novel derivatives based on 6-methyluracil and condensed uracil, 2,4-quinazoline-2,4-dione, were synthesized with terminal meta- and para-benzoate moieties in polymethylene chains at the N atoms of the pyrimidine ring. In the synthesized compounds, the polymethylene chains were varied from having tris- to hexamethylene chains and quaternary ammonium groups; varying substituents (ester, salt, acid) at benzene ring were introduced into the chains and benzoate moieties. In vivo biological experiments demonstrated the potency of these compounds in decreasing the number of β-amyloid plaques and their suitability for the treatment of memory impairment in a transgenic model of Alzheimer’s disease.

New morpholinium surfactants with a carbamate fragment between the amphiphile head group and its hydrophobic tail (C _n MB-carb, where n = 8, 10, 12, 14, 16) were synthesized. The cmc values obtained by tensiometry for dodecyl, tetradecyl, and hexadecyl homologues are 3–4 times lower than those of 4-alkyl-4-methylmorpholinium bromides. The introduction of a carbamate fragment can be considered as tool for controlling cmc values. The calculation of the thermodynamic parameters of micellization, i.e., Gibbs free energy of micellization (∆ G _mic ), enthalpy of micellization (Δ H _mic ), entropy of micellization (Δ S _mic ), were carried out based on the temperature dependences of specific electrical conductivity as a function of surfactant concentration. It was determined that the aggregation of cationic surfactants is driven by the entropy and Δ G (CH ₂ ) is equal to 3.26 kJ/mol. The cmc values determined by fluorimetry were approximately two times lower than those obtained by tensiometry and conductometry, probably due to the ability to identify premicellar aggregates. Using the spectrophotometry, a twofold increase in the solubilization capacity of C ₁₆ MB-carb (0.036 mol _OOT /mol _surf ) was established in comparison with a non-functionalized morpholinium surfactants with the same tail length (0.019 mol _OOT /mol _surf ). The “closed bottle test” showed that the degree of C _n MB-carb biodegradation reaches 56.7–62.3%. It was found that the antimicrobial activity of the surfactants increases with the lengthening of the hydrocarbon tail with maximum activity for the tetradecyl homologue. In addition, dose-dependent activity of C ₁₄ MB-carb and C ₁₆ MB-carb on the cell wall, cell membrane, and membrane potential of Staphylococcus aureus was shown.