The possibility of the formation of amino-substituted derivatives [B10H9N(MBzim)CH2MBzim]2- (MBzim is 1-methylbenzimidazole) and [B10H9N+H(MBzim)CH2Bzid-]2- (Bzid is benzimidazolide) during the cadmium(ii) complexation with N,1-bis(1-methylbenzimidazol-2-yl)methanimine (L1) and N-(benzimidazol-2-yl)-1-(1-methylbenzimidazol-2-yl)methanimine (L2) with a -CH 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 N- linker group in the presence of a closo-decaborate anion has been demonstrated for the first time. The substitution likely results from the metal-promoted formation of the carbocation [Cd(MBzim)HC+-N-R]2+ (R = MBzim or Bzim), which acts as an electrophilic inducer in the EINS reaction with the [B10H10]2- anion. As a result, binuclear complexes {Cd(CH3CN)[B10H9N(MBzim)CH2MBzim]}2 and {Cd(DMF)[B10H9N+H(MBzim)CH2Bzid-]}2 have been obtained and characterized. A method for obtaining soluble salts Cat2[B10H9N(MBzim)CH2MBzim] and Cat2[B10H9N+H(MBzim)CH2Bzid-] (Cat = Na+, Bu4N+) has been proposed. The heteroleptic complex {CdL2(DMF)[B10H10-kappa 3B1,B2,B3]}, in which the benzimidazole derivative acts only as a ligand, has been obtained and characterized as a result of complexation with 1-isopropyl-N-((1-methyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-benzo[d]imidazol-2-amine (L3) with a -CH2-NH- linker group. X-ray diffraction analysis revealed the structural features of the synthesized compounds, namely the coordination of bis(benzimidazoles) resulting in the formation of a seven-membered chelate ring, and the facial coordination of the closo-decaborate anion, which is rare for cadmium(ii).

A systematic study of silver(I) complexation with benzimidazole containing compounds L: imines Bz-CH=N-C6H5 (L1: Bz is 1-methylbenzimidazole, C6H5 is phenyl; L2: Bz is 1-benzylbenzimidazole, C6H5 is phenyl) and amines Bz-CH2-NH-X (L3: Bz is 1-methylbenzimidazole, X is 4-metoxyphenyl (C6H4OCH3), L4: Bz is 1-benzylbenzimidazole, X is 4-chlorophenyl (C6H4Cl)) has been carried out. The effect of the ratio of the initial reagents Ag+: L, the type of linker group or substituent at the nitrogen atom of the imidazole ring in the organic ligand on the composition and structure of the resulting compounds has been determined. Benzimidazolecontaining mononuclear molecular silver(I) complexes [AgL1(CH3CN)NO3] (1), [Ag(L1)2NO3] (2), [AgL2NO3] (3), as well as mononuclear cationic complexes in the composition of salts [AgL2]NO3 (L = L2 (4), L3 (5), L4 (6)) have been obtained and characterized. The structural features of the synthesized compounds have been analyzed based on X-ray diffraction analysis data.

Silver(I) complexation with substituted (benzoimidazol-2-yl)methanamines Bz–CH2–NH–R (Bz is 1-methylbenzimidazole, R is anisole (L1) or 1-isopropylbenzimidazole (L2)) in the presence of boron cluster anions [BnHn]2– (n = 10, 12) has been studied for the first time. The influence of substituent R in the benzimidazole derivative on the composition and structure of the resulting compounds has been determined. Coordination compounds [Ag(L1)2]xAn (x = 1, An = Ag[B10H10]mm–; x = 2, An = [B12H12]2–), featuring closo-borate anions in the outer coordination sphere and monodentately coordinated ligands L1, have been synthesized and structurally characterized. Additionally binuclear complexes [Ag2(L2)2[µ-BnHn]] have been obtained, in which L2 is coordinated bidentately, forming a seven-membered metallacycle, while anions [BnHn]2– (n = 10, 12) act as bridging ligands. The structural features of the synthesized compounds have been analyzed, including the coordination mode of the organic ligands and the occurrence of positional and bond isomerism in compounds with coordinated boron cluster anions.

In the present work, 14 new diazepinobenzimidazole derivatives (DAB series) were screened for inhibitory activity against NMDA- and Ca2+-impermeable (CI) AMPA-receptors. Experiments were conducted on isolated Wistar rat neurons; pyramidal neurons of the CA1 zone of the hippocampus were used to study NMDA- and CI-AMPA-receptors. Cell isolation was performed by vibrodissociation; currents were recorded by whole-cell patch-clamp method. All the studied compounds at a concentration of 100 µM inhibited NMDA-receptors (≥30 four compounds: DAB-8, DAB-12, DAB-19, and DAB-32. DAB-8, DAB-12 and DAB-32 have a 4-substituted phenacyl group at the nitrogen atom N11 with an electronegative fluorine atom in the para position (DAB-8 and DAB-32) or without it (DAB-12), whereas the most active compound DAB-19 has a 4-tert-butyl-benzyl group at atom N11 with a bulky tert-butyl substituent in the para position. The most active of them were DAB-12, DAB-19, and DAB-32, which were studied further for their IC50 values. Compound DAB-19 demonstrated the most pronounced activity against both NMDA- and CI-AMPA-receptors: IC50 values were 11.0 ± 1.6 µM and 15.4 ± 1.4 µM, respectively. Such an ability to inhibit both NMDA- and CI-AMPA-receptors at such concentrations is quite remarkable. Based on previous data on the neuropsychotropic effects of DAB-19, we put forward hypothesis about its possible anticonvulsant activity, which was confirmed in the “Pentylenetetrazol Seizure” test. The identification of DAB-19 as a combined antagonist of NMDA- and CI-AMPA-receptors is an important achievement for the further development of effective anticonvulsants.

Introduction: Previous studies have examined the anxiolytic properties of compounds containing mutually annulated systems of 5H-2,3-benzodiazepine and [1,2,4]triazole, namely 7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine derivatives. In the present work, another group of 5H-2,3-benzodiazepine and 5H-[1,2,5]triazepine derivatives was examined for psychotropic activity. Materials and Methods: For in silico assay the PASS online test system and ADMET analysis were used. Compounds under study were also tested in vivo in Elevated Plus Maze, Open Field and Rotarod tests. Results and Discussion: Of note is that the presence of a 3,4-dimethoxyphenyl substituent at position 4 of the diazepine ring (RD-1, RD-7) leads to a decrease in anxiolytic activity compared to 4-methoxyphenyl derivatives (RD-6, RD-9). Among the derivatives of condensed 5H-[1,2,5]triazepines, a more pronounced anti-anxiety effect was exerted by compound RD-8 with an annelated benzimidazole bicycle compared to its analog RD-15 with a pyrrole cycle. The high anxiolytic activity of the compounds is facilitated by the presence of slightly branched (RD-6, RD-9) or unbranched (RD-8) substituents in position 4 of the diazepine or triazepine cycle. In the Rotarod test, it was noted that 4-(3,4-dimethoxyphenyl)-1-hydrazino-5H-2,3-benzodiazepine (RD-1) and 4-hydrazino-7,8,9-trimethyl-1-phenyl-5H-pyrrolo[2,1-d][1,2,5]triazepine (RD-15) have a negative effect on muscle tone in mice due to the presence of a hydrazino group in their composition. According to ADMET analysis, compounds RD-6, RD-8 and RD-9 are low toxic; however, a specific toxicity study among these derivatives is recommended. Conclusion: The most active and safe compound for further studies among the studied derivatives with a single administration is 1,4-diphenyl-5H-[1,2,5]triazepino[5,4-a]benzimidazole (RD-8) at a dose of 1.3 mg/kg.

A new method for the construction of the pyrido[3',2':4,5]imidazo[1,2-b]pyridazine system involves the use of 2-chloro-3-nitropyridine and 6-chloropyridazin-3(2H)-one as the starting reactants. The key step is the POCl3-promoted cyclization of the intermediate 2-(3-aminopyridin-2-yl)-6-chloropyridazin-3(2H)-one. The 2-positioned chlorine atom in the thus obtained 2-chloropyrido[3',2':4,5]imidazo[1,2-b]pyridazine can be replaced by a variety of nucleophiles.

Silver(I) complexation with boron cluster anions [BnHn]2- (n = 10, 12) and chelating 1-substituted-2-aldiminebenzimidazoles 1-(1-methylbenzimidazol-2-yl)-N-phenylmetanimine (L1) and 1-(1-benzylbenzimidazol-2-yl)-Ncyclohexylmethanimine (L2) in systems AgNO3/[BnHn]2- /L and {Ag2[BnHn]}m/L, as well as with azaheterocyclic ligands 2,2'-bipyridine (bipy) or 1,10-phenanthroline (phen) in the system AgNO3/[BnHn]2- /L has been first studied. The effect of the organic ligand on the composition and structures of the resulting compounds has been shown. As a result, binuclear complexes [Ag2L2[mu-BnHn]] with bridging boron cluster anions with various combinations of coordination modes (edge-edge and edge-face for the [B10H10]2- anion, edge-atom and nontrivial asymmetric for the [B12H12]2- anion) have been synthesized and structurally characterized for benzimidazole derivatives L1 and L2. When using bipy or phen as ligands, polymeric complexes {Ag2L[B10H10]}m or {Ag2L2[mu-B12H12]}m have been obtained.

Janus kinase 2 (JAK2), one of the JAK isoforms participating in a JAK/STAT signaling cascade, has been considered a potential clinical target owing to its critical role in physiological processes involved in cell growth, survival, development, and differentiation of various cell types, especially immune and hematopoietic cells. Substantial studies have proven that the inhibition of this target could disrupt the JAK/STAT pathway and provide therapeutic outcomes for cancer, immune disorders, inflammation, and COVID-19. Herein, we performed docking-based virtual screening of 63 in-house furopyridine-based compounds and verified the firstround screened compounds by in vitro enzyme- and cell -based assays. By shedding light on the integration of both in silico and in vitro methods, we could elucidate two promising compounds. PD19 showed cytotoxic effects on human erythroblast cell lines (TF -1 and HEL) with IC50 values of 57.27 and 27.28 mu M, respectively, while PD12 exhibited a cytotoxic effect on TF -1 with an IC50 value of 83.47 mu M by suppressing JAK2/STAT5 autophosphorylation. In addition, all screened compounds were predicted to meet drug-like criteria based on Lipinski's rule of five, and none of the extreme toxicity features were found. Molecular dynamic simulations revealed that PD12 and PD19 could form stable complexes with JAK2 in an aqueous environment, and the van der Waals interactions were the main force driving the complex formation. Besides, all compounds sufficiently interacted with surrounding amino acids in all crucial regions, including glycine, catalytic, and activation loops. Altogether, PD12 and PD19 identified here could potentially be developed as novel therapeutic inhibitors disrupting the JAK/STAT pathway.

Carbonic Anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide involved in several biological processes. They show a wide diversity in tissue distribution and their subcellular localization. Twenty‐two novel phthalazine derivatives were designed, synthesized, and evaluated against four human isoforms: hCA I, hCA II, hCA IX, and hCA XII. Compounds appeared to be very active mostly against hCA IX (7) and hCA I (6) isoforms being more potent than reference drug acetazolamide (AAZ). Some compounds appeared to be very selective with a selectivity index up to 13.8. Furthermore, docking was performed for some of these compounds on all isoforms to understand the possible interactions with the active site. Additionally, the most active compounds against hCA IX were subjected to cell viability assay. The anticancer activity of the compounds (3a–d, 5d, 5i, and 5m) was investigated using two human breast cancer cell lines, i.e. MCF‐7 and MDA‐MB‐231 cells, and the normal counterpart, namely MCF10‐A cells.

The treatment of patients with nonsmall cell lung cancer (NSCLC) using epidermal growth factor receptor (EGFR) inhibitors is complicated by drug-sensitive activating L858R/T790M and L858R/T790M/C797S mutations. To overcome drug resistance, a series of furopyridine (PD) compounds were virtually screened to identify potent EGFR inhibitors using molecular docking and molecular dynamics (MD) simulations based on the solvated interaction energy (SIE) method. Several PD compounds identified from virtual screening demonstrated the potential to suppress both wild-type and mutant forms of EGFR, with IC50 values in the nanomolar range. Among these, PD18 and PD56 exhibited highly potent inhibitory activity against both wild-type and mutant forms of EGFR, surpassing the efficacy of known drugs. Additionally, both PD compounds were cytotoxic to NSCLC cell lines (A549 and H1975) while being nontoxic to normal cell lines (Vero). The interaction mechanisms of both PD compounds complexed with wild-type and mutant forms of EGFR were elucidated through 500 ns molecular dynamics simulations. The predicted binding affinity from molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) correlated well with the experimental binding affinity derived from IC50 values. Furthermore, it was observed that van der Waals interactions, rather than electrostatic interactions, played a significant role in interacting with EGFR's active site. The strong inhibitory activity against EGFR was attributed to two key residues, M793 and S797, via hydrogen bonding, corresponding with lower solvent accessibility and a higher number of atomic contacts. Therefore, these potent compounds could be developed as promising drugs targeting both wild-type and mutant EGFR for the treatment of NSCLC.

Representatives of previously unknown benzimidazole-2-carbothioamides containing N-β-(hetero)arylethyl groups in the thioamide fragment were synthesized. Such structures are interesting as agents with anti-infective, neuro(psycho)tropic and anticancer activity. It was shown that some representatives with an additional highly basic site in the N-substituent can show high protistocidal activity.

Novel β-arylethylamines bearing 5-pyrazolone substituent in the ortho-position of aryl moiety were obtained by the hydrazine-induced recyclization of 1-(alkoxycarbonyl-methylidene)-1,2,3,4-tetrahydroisoquinolines. These amines can exist in a highly unstable betaine form in the solid phase.

A cyclization–recyclization pathway for indirect 2-heteroarylation of tryptamines has been suggested by the example of introducing the pyrazolyl moiety. The process involves the intermediate cyclization of tryptamines into push–pull type β-carboline semi-products. The relative stability of the tautomeric forms of 2-pyrazolyltryptamines has been estimated using the DFT method.

Targeting L858R/T790M and L858R/T790M/C797S mutant EGFR is a critical challenge in developing EGFR tyrosine kinase inhibitors to overcome drug resistance in non-small cell lung cancer (NSCLC). The discovery of next-generation EGFR tyrosine kinase inhibitors (TKIs) is therefore necessary. To this end, a series of furopyridine derivatives were evaluated for their EGFR-based inhibition and antiproliferative activities using computational and biological approaches. We found that several compounds derived from virtual screening based on a molecular docking and solvated interaction energy (SIE) method showed the potential to suppress wild-type and mutant EGFR. The most promising PD13 displayed strong inhibitory activity against wild-type (IC50 of 11.64 ± 1.30 nM), L858R/T790M (IC50 of 10.51 ± 0.71 nM), which are more significant than known drugs. In addition, PD13 revealed a potent cytotoxic effect on A549 and H1975 cell lines with IC50 values of 18.09 ± 1.57 and 33.87 ± 0.86 µM, respectively. The 500-ns MD simulations indicated that PD13 formed a hydrogen bond with Met793 at the hinge region, thus creating excellent EGFR inhibitory activity. Moreover, the binding of PD13 in the hinge region of EGFR was the major determining factor in stabilizing the interactions via hydrogen bonds and van der Waals (vdW). Altogether, PD13 is a promising novel EGFR inhibitor that could be further clinically developed as fourth-generation EGFR-TKIs.

A series of Schiff base derivatives, namely N-(4-methoxyphenyl)-1-(1-methylbenzimidazol-2-yl)methanimine (L1), 4-methoxy-N-[(1-methylbenzimidazol-2-yl)methyl]aniline (L2), and 2-[(E)-(1-propylbenzimidazol-2-yl)iminomethyl]phenol (L3), were synthesized. These compounds feature different linker groups, including –CH=N–, –CH2–NH–, and –N=CH–, respectively. During the process of zinc(II) and cadmium(II) complexation in the presence of the closo-dodecaborate [B12H12]2– anion, it was observed that ligand L3 underwent degradation. Consequently, two compounds were isolated, [Zn(Bz-NH2)2(CH3COO)2] and (HBz-NH2)2[B12H12]∙2CH3CN, both containing 1-propyl-2-aminobenzimidazole (Bz-NH2), which is a degraded fragment of the ligand. Several new zinc(II) and cadmium(II) coordination compounds were synthesized and characterized using various physicochemical analysis methods, including elemental analysis, IR, and UV spectroscopy. Additionally, X-ray diffraction and Hirshfeld surface analysis were performed for compounds [Cd(L2)2(CH3CN)(H2O)][B12H12], [Zn(Bz-NH2)2(CH3COO)2], and (HBz-NH2)2[B12H12]∙2CH3CN, as well as for ligand L2.

New ligands, namely N-[(1-benzyl-1H-benzimidazol-2-yl)methylidene]aniline (L1) and its chloro-derivative N- [(1-(4 & PRIME;-chlorobenzyl)-1H-benzimidazol-2-yl)methylidene]aniline (L2), have been synthesized. Their behavior in the course of cadmium(II) complexation has been studied in the presence of the closo-decaborate anion [B10H10]2-. Mixed-ligand complexes [CdL2[B10H10]] (L = L1, L2) have been isolated, which contain the [B10H10]2- anion coordinated by the metal atom via three-center two-electron (3c2e) CdHB bonds. The structures of both complexes have been determined by single-crystal X-ray diffraction. Based on the data of the UV-vis absorption spectra measured for the synthesized compounds, it has been concluded that the luminescent prop-erties are retained in the complexes under consideration. The intensity of the luminescence and the position of the emission band of the cadmium(II) complexes have been analyzed. Quantum-chemical calculations based on density functional theory (DFT) calculations have allowed us to determine the general relationships between the structural and spectroscopic characteristics.

Осуществлен синтез комплекса Co(II) на основе 1-{1-[2-(о-толилокси)этил]-1Н-бензимидазол-2-ил}этан-1-ола. Методами элементного анализа и ИК спектроскопии установлено, что состав комплекса кобальта [Co(L)3]2+·2(NO3)–·2H2O·2CH3OH. Его кристаллическое строение определено методом рентгеноструктурного анализа монокристалла. Из данных РСА установлено, что комплекс кристаллизуется в моноклинной пространственной группе P21/c. В моноядерной молекуле комплекса к катиону Co(II) координированы три хелатных лиганда атомами O гидроксильной группы и атомами N имидазольного цикла. Координационное окружение атома кобальта CoN3O3 соответствует искаженному октаэдру.

The anxiolytic effect of a new series of C2,C3-quinoxaline derivatives was studied using the "Anxious-phobic state" and "Light/Dark chamber" techniques in comparison with diazepam. It was noted that the presence of a phenyl substituent at the C3 position, which did not contain elements with a distinct electronegativity, as well as 2-methyl-(4,5-dimethoxyphenyl)-N-methylethane-1-amine at the C2 position, had a positive effect on the manifestation of the antianxiety activity of new derivatives of C2,C3-quinoxaline. For the most active compound under the code ZDM-4, the conflict method "Vogel Conflict test" was additionally carried out to confirm the anxiolytic effect of the substance. The tranquiLizing potential of the ZDM-4 compound is of interest for further study.

Zinc(II) and cadmium(II) complexation with the dodecahydrido-closo-dodecaborate anion [B12H12]2– in the presence of benzimidazole ligands 1-methylbenzimidazo-2-yl-methyleneaniline (L1) and 1-ethyl-2-(4-methoxyphenyl)azobenzimidazole (L2) was studied. A number of Zn(II) and Cd(II) complexes with the [B12H12]2– anion and ligands L1 or L2 were obtained and characterized. Effect of the metal nature on the composition and structure of the resulting compounds was determined. Only tris-chelate zinc(II) complexes with the [B12H12]2– anion were isolated. For cadmium, first examples of mixed-ligand complexes with the [B12H12]2– anion coordinated by the metal atom via 3c2e (CdHB) bonds were isolated. Structures of complexes [Zn(L1)3][B12H12]·2CH3CN, [Cd(L1)2[B12H12]]·2CH3CN and [Cd(L2)2(CH3CN)[B12H12]]·CH3CN were determined by X-ray diffraction.