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1.
J Org Chem ; 84(21): 13572-13581, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31549510

RESUMO

A novel and efficient protocol for the synthesis of diversely substituted 2,2'-bibenzimidazoles from the reaction of 3-cyanoquinoxalin-2(1H)-ones with 1,2-diaminobenzenes has been developed, which proceeds through sequential nucleophilic addition and electrophilic substitution followed by a Mamedov rearrangement. The synthetic utility of this strategy was illustrated by the concise, one-pot synthesis of 5,5'-bi(2,2'-bibenzimidazoles) and aza-analogues of 2,2'-bibenzimidazole.

2.
J Phys Chem B ; 123(26): 5514-5523, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31192599

RESUMO

We report on the electronic absorption spectra, conformational behavior, and intra- and intermolecular hydrogen bonds of 2,3-(dibenzimidazol-2-yl)-quinoxaline (DBIQ). The experimentally found strong solvent dependence of the absorption spectra of DBIQ solutions cannot be assigned to electronic excitations of the equilibrium ground-state DBIQ structure. Extended consideration including the nonequilibrium structures within the framework of ab initio molecular dynamics (MD) revealed the importance of torsion molecular motions not covered by the static case. The strong impact of solute-solvent hydrogen bonding on stabilization of these nonequilibrium structures and on conformational composition of DBIQ was demonstrated. A presence of twisted nonplanar geometries along the whole MD trajectory was shown to drastically influence not only energies but also characters of electronic excitations, resulting in a change of local π-π* character in a solution of 1,2-dichloroethane to charge-transfer character in polar dimethylsulfoxide.

3.
Colloids Surf B Biointerfaces ; 178: 317-328, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30884347

RESUMO

Multi-targeted approaches for inhibition of сervical cancer cells in vitro were developed by implementing two different strategies and drug combination for creation of new therapeutic target agents and for nanotechnological-enhancement of intracellular delivery. New 2-benzimidazolylquinoxalines derivatives were synthesized and characterized by combining two different pharmacophores - benzimidazole and quinoxaline rings directly bonded in their structures. Spectrophotometric technique for determination of content of compounds in various media was developed to evaluate their solubility in water and micellar solutions of surfactants. The bioavailability of poorly water-soluble 2-benzimidazolylquinoxalines was improved by PEGylated liposomes as antitumor drug delivery carriers. 2-benzimidazolylquinoxalines-loaded PEGylated liposomes, with size close to 100 nm and negative zeta potential ranging from -13 mV to -27 mV, were time-stable at room temperature. The design of liposomal formulations for improving cellular uptake and in vitro antitumor efficacy was performed by modification of liposome surface with the new arginine surfactant. The cell viability of 2-benzimidazolylquinoxalines-loaded arginine liposomes on human cancer M-Hela cells was 16% at the concentration 0.15 mg/ml. Moreover, these liposomes showed a lower toxicity (40%) against normal human Gang liver cells both at the lowest and highest tested concentrations.


Assuntos
Arginina/química , Sistemas de Liberação de Medicamentos/métodos , Lipossomos/química , Quinoxalinas/química , Células HeLa , Humanos , Tensoativos/química
4.
J Org Chem ; 83(24): 14942-14953, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30431276

RESUMO

A facile approach to a range of substituted 7-(benzimidazol-2-yl)thioxolumazines [7-(benzimidazol-2-yl)-2-thioxo-2,3-dihydropteridin-4(1 H)-ones] and 7-(benzimidazol-2-yl)lumazines [7-(benzimidazol-2-yl)pteridine-2,4(1 H,3 H)-diones] is described. These new biheterocyclic systems are obtained via H2SO4-catalyzed rearrangement of quinoxalin-2-ones in the presence of 5,6-diamino-2-mercapto- and 2,5,6-triaminopyrimidin-4-ols. Thus, benzimidazole and pteridine rings are constructed in one synthetic step. A plausible ANRORC ( addition of nucleophile, ring opening and ring closure)-type reaction mechanism is proposed. Applying the rearrangement to the aza-analogue of 3-benzoylquinoxalin-2(1 H)-one-i.e., 3-benzoylpyrido[2,3- b]pyrazin-2(1 H)-one-with 5,6-diamino-2-mercaptopyrimidin-4-ol makes it possible to synthesize inaccessible 7-(1 H-imidazo[4,5- b]pyridin-2-yl)-6-phenyl-2-thioxo-2,3-dihydropteridin-4(1 H)-one. 7-(Benzimidazol-2-yl)-6-(2-fluorophenyl)-2-thioxo-2,3-dihydropteridin-4(1 H)-ones undergoes intramolecular nucleophilic substitution of fluorine by a nitrogen of the benzimidazole fragment with the formation of benzo[4',5']imidazo[1',2':1,2]quinolino[4,3- g]pteridine-2,4(1 H,3 H)-diones as new heterocyclic systems.

5.
J Org Chem ; 83(21): 13132-13145, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30272451

RESUMO

The new efficient synthesis of biologically important 3-hydroxy-4-arylquinolin-2-ones through the Darzens condensation (epoxidation) of dichloroacetanilides with aromatic aldehydes followed by one-pot dechlorative epoxide-arene cyclization is described. This methodology has been utilized for the synthesis of naturally occurring viridicatol, a fungal metabolite isolated from the penicillium species.

6.
Phys Chem Chem Phys ; 19(8): 6095-6104, 2017 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-28191569

RESUMO

We report on the photophysical properties, conjugation, conformational behavior, intra- and intermolecular hydrogen bonds (HBs) of a series of novel fluorophores, consisting of 3-arylquinoxaline and benzimidazole moieties linked by a single CC bond. Computations employing density functional theory (DFT) reveal that conjugation between these moieties stabilizes syn-conformers with two HB centers located on the same side of the molecule. Anti-conformers form stronger intermolecular HBs with DMSO and DMF than syn-conformers, and this influences the energy gap between syn- and anti-forms, especially upon excitation of the molecules to the S1 state. Substituents introduced in various positions of the molecules modify their conformational behavior, and mutual disposition of excited singlet states relative to the ground states. Various substitution patterns produce very different effects on relative quantum yield of luminescence: from a moderate increase in polar DMSO and DMF relative to 1,2-dichloroethane solutions to complete quenching of emission which is observable in polar media. The observed behavior is understood with the aid of DFT and time-dependent DFT calculations. The tuneability of the spectroscopic range of the luminescence and especially of its sensitivity to environmental effects allows rational design of the novel fluorophores of this family for various applications.

7.
J Org Chem ; 80(3): 1375-86, 2015 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-25496019

RESUMO

The reaction of 3-benzoylquinoxalin-2(1H)-ones with enamines (generated in situ from ammonium acetate and the corresponding methylaryl(hetaryl)ketones) proceeds smoothly to give the corresponding substituted 1-(pyrrolyl)benzimidazolone derivatives in moderate yields through the novel rearrangement of 3-benzoylquinoxalin-2(1H)-ones involving a dual cleavage of the C3═N4 and C2-C3 bonds under mild conditions.


Assuntos
Acetatos/química , Aminas/química , Benzimidazóis/química , Benzimidazóis/síntese química , Cetonas/química , Quinoxalinas/química , Catálise , Estrutura Molecular , Estereoisomerismo
8.
J Org Chem ; 79(19): 9161-9, 2014 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-25203611

RESUMO

A synthetically useful protocol has been developed for the preparation of highly functionalized N-pyrrolylbenzimidazol-2-ones. The reaction of variously substituted 3-aroyl- and 3-alkanoylquinoxalin-2(1H)-ones with commercially available enamines in acetic acid results in a rapid rearrangement and formation of N-pyrrolylbenzimidazol-2-ones in modest to excellent yields. The key step of the rearrangement involves the novel ring contraction of 3-aroyl- and 3-alkanoylquinoxalin-2(1H)-ones with enamines. In this case, the atom of carbon which is displaced from the pyrazine ring of quinoxalin-2(1H)-one becomes the fourth carbon atom of the newly formed pyrrole ring. The method is applicable for the aza analogues of quinoxalin-2(1H)-ones.


Assuntos
Compostos Aza/química , Benzimidazóis/síntese química , Piridonas/síntese química , Quinoxalinas/química , Benzimidazóis/química , Estrutura Molecular , Piridonas/química , Relação Estrutura-Atividade
9.
Eur J Med Chem ; 66: 345-54, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23811259

RESUMO

3-Phenyl(methyl)-5-alkyl-1-(pyridin-3-yl)imidazo[1,5-a]quinoxalin-4-ones (2a-f) and their N-alkyl-pyridinium salts (3a-o), including 1,n-bis{3-(3-phenylimidazo[1,5-a]quinoxalin-4(5H)-on-1-yl)pyridinium}alkane dibromides (4a-d, 5, 6) have been synthesized. It has been established that the antimicrobial properties of imidazo[1,5-a]quinoxaline derivatives are connected with the presence of various alkyl substituents in the position 1 of the pyridine ring and in the position 5 of the imidazo[1,5-a]quinoxaline system. Chlorides and iodides are more active towards bacteria than fungi. Compounds 3d, 3e, 3m and 3n showed an effective bacteriostatic activity. Compound showed not only well defined bacteriostatic activities but also good fungistatic activities, with the MIC values comparable with the reference drugs. Toxicity of more effective (imidazo[1,5-a]quinoxalin-4-on-1-yl)-1-pyridinium halides was examined in mice.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Compostos de Piridínio/química , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/toxicidade , Bactérias/efeitos dos fármacos , Desenho de Fármacos , Feminino , Fungos/efeitos dos fármacos , Imidazóis/síntese química , Imidazóis/toxicidade , Masculino , Camundongos , Testes de Sensibilidade Microbiana
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