Russian Journal of General Chemistry最新文献

By reaction between acetylbenzenesulfonamides with several substituted isatins, we have synthesized a series of 22 primary sulfonamides, 16 of which were tested for inhibition activity against MAO-A and MAO-B. At the same time, in order to diversify the resulting structures, we have carried out decarboxylation as well as further functionalization at the carboxylic acid. The results of the study show that methyl 6-chloro-2-(3-sulfamoylphenyl)quinoline-4-carboxylate selectively inhibited MAO-B with a value of IC₅₀ = 13.7 μM.

A series of 2-thiopyrimidines and thiopyrans were prepared by the reaction of the corresponding α,β-unsaturated ketones with thiourea and Lawesson’s reagent, respectively. The synthesized compounds were characterized by spectral analysis and screened for antimicrobial and antioxidant activity. The antimicrobial activity was examined in vitro against gram-positive, gram-negative bacteria and yeast where the results showed that gram-positive bacteria were more susceptible to the tested compounds than gram-negative bacteria and yeast. Among all the compounds evaluated for antioxidant activity, four compounds showed the highest activity (97, 96, 95, and 89%). In silico molecular docking, investigations were undertaken to validate the antibacterial results. The molecular docking results were compatible with the in vitro antibacterial findings.

A series of novel lupeol-3-urea/thiourea derivatives were designed, synthesized and evaluated for their in vitro anticancer activity against human lung cancer A549, human hepatocellular carcinoma HepG2 and human breast cancer MCF-7 cell lines. The antitumor activities of all compounds were higher than that of parent Lupeol. Among them, lup-20(29)-en-3β-yl-piperazinecarboxylate-(2,4-fluorophenyl)urea showed the strongest antitumor activity against A549 cell lines, with an IC₅₀ of 3.22 μM, which is tenfold than that of Lupeol. Therefore, lup-20(29)-en-3β-yl-piperazinecarboxylate-(2,4-fluorophenyl)urea can be used as a new lead compound for the development of more potent antitumor drugs.

Previously unknown betulin and allobetulin derivatives, which are of interest as potential biologically active substances, were synthesized by replacing chlorine in 3,28-bis(chloroacetoxy)betulin and 3-chloroacetoxyallobetulin with pharmacophoric cycloheteryl sulfide groups.

The ability of alkylisothiuronium bromides (C_nSUBr) and 7-chloro-4,6-dinitrobenzofuroxan-5-olates (C_nSUBf) to incorporate into lipid bilayer was assessed. It was established that the transition from the decyl to the hexadecyl homologue results in bilayer stabilization, as evidenced by an increase in the phase transition temperature of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine. Liposomes based on soy phosphatidylcholine and cholesterol were modified with representatives of both homologous series at various molar ratio of surfactant to lipid (1 : 50, 1 : 35, 1 : 20). The zeta potential of liposomes modified with C_nSUBr at all surfactant/lipid ratio was higher than that of liposomes modified with C_nSUBf. The liposomes were visualized using transmission electron microscopy. Hydrophilic substrate rhodamine B was successfully loaded into cationic liposomes with high encapsulation efficiency (over 89%). The most prolonged release of rhodamine B in vitro was observed from liposomes modified with C₁₆SUBr and C₁₆SUBf. Using the Korsmeyer–Peppas mathematical model, it was established that the release of rhodamine B from liposomes occurred through a mixed mechanism of substrate diffusion and destabilization of the phospholipid bilayer of liposomes.

New morpholinium surfactants with a carbamate fragment between the amphiphile head group and its hydrophobic tail (C_nMB-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 (ΔH_mic), entropy of micellization (ΔS_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 ΔG(CH₂) 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 C₁₆MB-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_nMB-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 C₁₄MB-carb and C₁₆MB-carb on the cell wall, cell membrane, and membrane potential of Staphylococcus aureus was shown.

A new approach for the preparation of 3-alkenyl furans and thiophenes by selective C³–H alkenylation of furan-2- and thiophene-2-carboxylic acids with internal alkynes has been developed, and novel 3-alkenylated furans and thiophenes have been synthesized and characterized. The main advantages of the developed approach are the use of readily available substrates in which the COOH function serves as a traceless in situ removable directing group, the high regioselectivity of the C³–H alkenylation, which provides easy access to C³-alkenylated furans and thiophenes with highly reactive C²–H and C⁵–H bonds that are difficult to access by previously reported methods, and the use of a relatively inexpensive [RuCl₂(p-cymene)₂] precatalyst in the absence of copper and silver promoters.

Polycyclic systems such as acenaphthylene, fluoranthene, benzo[k]fluoranthene, and indeno[1,2,3-c,d]pyrene were studied and their adsorption behavior on carbon-based tweezer (CT) compound was estimated. Geometrical optimization based on DFT approach was considered, and molecular electrostatic potential (MEP) was mapped for further comparison between adsorption systems. Topological analysis such as reduced density gradient (RDG) in predicting the non-covalent interactions (NCI) at the adsorption surface was studied with a color map scale to characterize each interaction type. Absorbance evaluation through TD-DFT theory was involved to describe the optical behavior before and after adsorption. Molecular dynamic simulation was studied through 100 ps for some stability comparison between studied systems where temperature results full within 1250 to 1550 K for the four adsorption systems. The interaction on the CT surface was described by performing adsorption annealing module and the adsorption process mainly depended on the planar-like geometrical system for best surface interaction. The adsorption energy parameter for some estimated models can control the strength of interaction on the surface of CT compound. A benchmark study to compare the more suitable functional for adsorption systems description was performed using CAM-B3LYP/6-311++G functional and confirmed the more precise involved method with BBSE consideration.

The effect of the polysaccharide:protein mass ratio, pH, concentration, and nature of the inorganic salt (sodium and calcium chlorides) on the phase behavior of aqueous mixtures of porcine gelatin with kappa-, lambda-, or iota-carrageenans was studied using turbidimetric titration. The formation of insoluble protein-polysaccharide complexes was observed in the range of pH between two boundary values, which decreased with increasing polysaccharide–protein mass ratio (Z). An increase in the number of sulfate groups in the polysaccharide in the series kappa- < iota- < lambda-carrageenan leads to a decrease in the boundary pH values at constant Z. Electrostatic interactions between gelatin and carrageenan molecules are suppressed with increasing ionic strength, which leads to the destruction of insoluble complexes upon addition of salts.

This study introduces a group of substituted pyrazolo[4,5-a]quinindolines and imidazo[4,5-a]quinindolines as potent inhibitors of acetylcholinesterase (AChE). The compounds were synthesized through a one-pot reaction of 1-alkyl-5-nitro-1H-indazole and 1-alkyl-5-nitro-1H-benzimidazole derivatives with 2-(1-alkyl-1H-3-indolyl)acetonitriles in alkaline conditions. Experimental methods such as FT-IR, MS, ¹H and ¹³C NMR spectral analysis were used to characterize the newly synthesized compounds. The catalytic activity of the enzyme was evaluated in the presence of pyrazolo[4,5-a]quinindolines and imidazo[4,5-a]quinindolines, and the mixed inhibition model determined the reversible enzyme-inhibitor complex’s inhibition constants to be between 0.069‒0.116 mM. Also, molecular modeling techniques were used to identify the specific amino acid residues in the active site of the enzyme that interact with certain ligands. The presence of these ligands caused some regions of the AChE residues to become less flexible. The analysis revealed that the ligands bind with the active site of the AChE enzyme.