Serotonin, or 5-hydroxytryptamine (5-HT), is a biogenic amine most noted as a neurotransmitter, an activator of the utmost subtype family of G-protein- coupled receptors (GPCR). Drugs targeting 5-HT1A and other 5-HT receptors treat central nervous system diseases such as schizophrenia and depression. Recent advances in serotonin receptor structure research gave us several crystal 5-HT1A receptor structures, most notably 5-HT1A bound to the antipsychotic drug aripiprazole (Abilify?). This discovery prompted us to evaluate a series of newly synthesized ligands for serotonergic activity since those arylpiperazine derivatives share minimal general structure with aripiprazole. The results of molecular docking analysis of unsubstituted starting substances encouraged us to propound further modifications of the tail and head parts of the parent molecules to maximize receptor binding affinity. Intrigued by the results of molecular analysis, all foreseen derivatives were synthesized. The pharmacological activity of all nine (5a and 6a are synthesized previously) compounds was assessed by the in vitro tests and in silico pharmacokinetics predictions for the most promising candidates. All tested ligands have improved affinity compering to parent compounds (10a and 11a), 8b and 9b expressed the best pharmacological profile with an improved binding affinity toward serotonin 5-HT1A receptors (Ki 12.1 and 4.8 nM, respectively).

Synthetic dyes from textile effluents represent a major environmental concern due to their persistence and toxicity. Reactive Black 5 (RB5) is widely used in the textile industry and is commonly applied as a model azo compound in sorption studies. This study comparatively evaluates the sorption performance of raw and carbonized sorbents derived from industrial hemp (Cannabis sativa L.) biowaste using an integrated experimental and theoretical approach. The sorbents were prepared through washing, drying, and phosphoric acid-assisted carbonization followed by pyrolysis. Structural and physicochemical properties were characterized using elemental analysis, FTIR spectroscopy, and SEM microscopy. Sorption performance toward RB5 was investigated through batch kinetic and equilibrium experiments, supported by kinetic (pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion models) and isotherm (Langmuir, Freundlich, and Temkin) modeling. Molecular docking simulations were performed to provide mechanistic insight into dye–sorbent interactions. Both materials exhibited rapid sorption kinetics, reaching equilibrium within approximately 45 min, with the pseudo-second-order model suggesting that surface-controlled interactions dominate the sorption rate. Molecular modeling, based on extensive conformational sampling, indicated a strong binding affinity between RB5 and cellulose-based structures, primarily associated with hydrogen bonding and other favorable noncovalent interactions. In contrast, graphene-based models revealed sorption governed by π–π interactions and confinement effects, supporting the experimentally observed differences between raw and carbonized sorbents.

The synthetic route toward novel tricyclic, nitrogen-containing system is disclosed. Three novel compounds possessing structural features of 1,2,3,4-tetrahydroquinoxaline and decahydropyrido[3,4-b]pyrazine are synthesized starting from readily available precursors in six or seven steps, of which the last three or four steps respectively are diastereoselective. Key reaction steps include N-acylation, Hofmann rearrangement and ring-closing Buchwald? Hartwig reaction. Compounds trans-8, cis-12 and trans-12 are synthesized in order to prove that this novel, tricyclic system can be functionalized with various groups. Synthetic significance of this heterocyclic system lies in the possibility for the orthogonal functionalization of three different amino groups, allowing fine structural tuning.

Two new tacrine/pyrazole conjugates were designed, synthesized, and pharmacologically evaluated for their inhibitory activity toward acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A scalable and cost-efficient synthetic route was developed, and key reaction steps for the synthesis of compounds 4a,b were nucleophilic substitution of α-aroylketene dithioacetals with tacrine intermediates, followed by cyclocondensation of respective N,S-acetals with hydrazine hydrate. The preliminary pharmacological evaluation revealed high inhibitory activities of 4a,b toward AChE (180 and 259 nM, respectively) and BuChE (51 and 95 nM, respectively) as compared with known inhibitor, tacrine. Overall, both compounds were more efficient BuChE inhibitors while 4a, with a shorter linker connecting tacrine and phenylpyrazole moieties, showed higher inhibitory activity toward both enzymes. Molecular docking analysis strongly corroborated pharmacological results since both compounds interacted favorably with target enzymes. Calculated pharmacokinetic properties (absorption, distribution, metabolism, and excretion (ADME) showed that 4a,b obey Lipinski’s rule of druglikeness and are promising lead compounds for the development of new drug candidates.