Syntheses of 3-(2-Nitrovinyl)-indoles, Benzo[]carbazoles, Naphtho[2,1-]carbazoles, and 1-Hydroxy-β-carbolines Lead to Identification of Antiproliferative Compounds Active under Hypoxia.

Herein, we describe a novel reaction between C-2-substituted indoles and 2-nitroacetophenones leading to a variety of indole-containing heterocyclic scaffolds. At 60 °C in AcOH with HSO as catalyst, C-2 aryl indoles give 3-(2-nitrovinyl)-indoles with high or geometric selectivity depending on the type of substrate utilized. These compounds undergo an electrocyclization process in a sealed vial in a microwave apparatus in DMF at 250 °C to give benzo[]carbazoles and naphtho[2,1-]carbazoles depending on whether the C-2 aromatic moiety is phenyl or naphthyl.

Metal-Free, PPA-Mediated Fisher Indole Synthesis via Tandem Hydroamination-Cyclization Reaction between Simple Alkynes and Arylhydrazines.

A new variant of Fisher indole synthesis involving Bronsted acid-catalyzed hydrohydrazination of unactivated terminal and internal acetylenes with arylhydrazines is reported. The use of polyphosphoric acid alone either as the reaction medium or in the presence of a co-solvent appears to provide the required balance for activating the C-C triple bond towards the nucleophilic attack of the hydrazine moiety without unrepairable reactivity loss of the latter due to competing amino group protonation. Additionally, the formal hydration of acetylenes to the corresponding ketones occurs under the same conditions, making it an alternative approach for generating carbonyl groups from alkynes.

6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies.

New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N'-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or via a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalondianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichloro- phenyl)-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was confirmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computational scheme.

Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles.

The β-carboline motif is common in drug discovery and among numerous biologically active natural products. However, its synthetic preparation relies on multistep sequences and heavily depends on the type of substitution required in the core of the desired β-carboline target. Herein, we demonstrate that this structural motif can be accessed with the microwave-assisted electrocyclic cyclization of heterotrienic aci (alkylideneazinic acid) forms of 3-nitrovinylindoles.

New 6'-Amino-5'-cyano-2-oxo-1,2-dihydro-1'-spiro[indole-3,4'-pyridine]-3'-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity.

The purpose of this work was to prepare new isatin- and monothiomalondiamide-based indole derivatives, as well as to study the properties of the new compounds. The four-component reaction of 5-R-isatins (R = H, CH), malononitrile, monothiomalonamide (3-amino-3-thioxo- propanamide) and triethylamine in hot EtOH yields a mixture of isomeric triethylammonium 6'-amino-3'-(aminocarbonyl)-5'-cyano-2-oxo-1,2-dihydro-1'- and 6'-amino-3'-(aminocarbonyl)- 5'-cyano-2-oxo-1,2-dihydro-3'-spiro[indole-3,4'-pyridine]-2'-thiolates. The reactivity and structure of the products was studied.

Alkyl 4-Aryl-6-amino-7- phenyl-3-(phenylimino)-4,7-dihydro- 3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxylates: Synthesis and Agrochemical Studies.

The reaction between dithiomalondianilide (N,N'-diphenyldithiomalondiamide) and alkyl 3-aryl-2-cyanoacrylates in the presence of morpholine in the air atmosphere leads to the formation of alkyl 6-amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]- pyridine-5-carboxylates in 37-72% yields. The same compounds were prepared in 23-65% yields by ternary condensation of aromatic aldehydes, ethyl(methyl) cyanoacetate and dithiomalondianilide. The reaction mechanism is discussed.

Stability of Dibromo-Dipyrromethene Complexes Coordinated with B, Zn, and Cd in Solutions of Various Acidities.

The spectral luminescent properties of dipyrromethenates halogenated with bromine on both ends of the long axis and coordinated using boron fluoride, zinc, or cadmium in neutral ethanol and acidified with hydrochloric acid solutions were studied. The constants of the acid-base equilibrium of the complexes in the proton-donor solvents in the ground and excited states was determined. The mechanisms of complex protonation were discussed, depending on the structure of the compounds.

The Reactions of N,N'-Diphenyldithiomalondiamide with Arylmethylidene Meldrum's Acids.

The Michael addition reaction between dithiomalondianilide (N,N'-diphenyldithiomalondiamide) and arylmethylidene Meldrum's acids, accompanied by subsequent heterocyclization, was investigated along with factors affecting the mixture composition of the obtained products. The plausible mechanism includes the formation of stable Michael adducts which, under the studied conditions, undergo further transformations to yield corresponding N-methylmorpholinium 4-aryl-6-oxo-3-(N-phenylthio-carbamoyl)-1,4,5,6-tetrahydropyridin-2-thiolates and their oxidation derivatives, 4,5-dihydro-3H-[1,2]dithiolo[3,4-b]pyridin-6(7H)-ones. The structure of one such product, N-methylmorpholinium 2,2-dimethyl-5-(1-(2-nitrophenyl)-3-(phenylamino)-2-(N-phenylthiocarbamoyl)-3-thioxopropyl)-4-oxo-4H-1,3-dioxin-6-olate, was confirmed via X-ray crystallography.

Nitrovinylindoles as Heterotrienes: Electrocyclic Cyclization En Route to β-Carbolines: Total Synthesis of Alkaloids Norharmane, Harmane, and Eudistomin N.

Unusual cascade transformation was developed involving microwave assisted electrocyclic cyclization of aci (alkylideneazinic acid) forms of nitrovinylindoles acting as heterotrienes. Subsequent one-pot reduction allowed for efficient access to β-carbolines, including several natural products, alkaloids norharmane, harmane and eudistomin N.

Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile -Methylmorpholinium Salt.

Sequential reaction of 2-chlorobenzaldehyde, cyanothioacetamide, and malononitrile dimer in the presence of an excess of -methylmorpholine resulted in the formation of -methylmorphlinium salt of 2-amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile. The resulting salt reacts under Mannich conditions with primary amines and an excess of formaldehyde to form substituted 2-alkylamino-4-(dicyanomethylene)-3,7-diazabicyclo[3.3.

,'-Diphenyldithiomalonodiamide: Structural Features, Acidic Properties, and In Silico Estimation of Biological Activity.

The spectral characteristics of dithiomalondianilide (,'-diphenyldithiomalonodiamide) were studied, and the dissociation constant was determined by potentiometric titration. Quantum-chemical methods at the B3LYP-D3BJ/6-311+G (2d,p) level were used to calculate the molecular geometry and vibrational spectra of the most stable tautomeric forms of dithiomalondianilide. The bioavailability parameters were calculated, and possible protein targets were predicted by the protein ligand docking method.

2-Amino-4,5-dihydrothiophene-3-carbonitriles: A New Synthesis, Quantum Chemical Studies, and Mannich-Type Reactions Leading to New Hexahydrothieno[2,3-d]pyrimidines.

-2-Amino-4-aryl-5-benzoyl-4,5-dihydrothiophene-3-carbonitriles were prepared either by the reaction of 3-aryl-2-cyanothioacrylamides with α-thiocyanatoacetophenone or by the Michael-type addition of cyanothioacetamide to α-bromochalcones followed by intramolecular cyclization. The mechanism of the first reaction was studied using high-level quantum chemical calculations. Density functional theory (DFT) studies were carried out to determine the mechanism of the first reaction.

Trends in Breast Cancer Epidemiology in Chelyabinsk Region, 2006-2015.

Breast cancer among women occupies a leading position in the profile of cancer incidence in most parts of the world. The present study of the incidence and prevalence of breast cancer was carried out using data from the Chelyabinsk population cancer registry for 2006-2015. A stable growth trend in the incidence over time was noted overall, as well as major differences in the figures for women of different ethnicities (Russian, Tatar, Bashkir), by far the highest incidences being observed for Russian women.

[Pathogenetic effects of low-intensity laser therapy for chronic obstructive pulmonary disease].

Aim: To study the impact of low-intensity laser therapy (LILT) on typical pathological processes of impairments in platelet aggregation and microcirculation (MC) in patients with chronic obstructive pulmonary disease (COPD).

Materials And Methods: A photo optical aggregatometric method was used to investigate platelet aggregation function in patients with COPD and MC was estimated by laser Doppler flowmetry over time.

Results: There were muitidirectional changes in platelet aggregation function with a predominance of hyperaggregation, as well as a significant improvement in aggregation indicators during LILT; the latter was shown to have a correcting impact on MC disorders in patients with COPD in the presence of the spastic and stagnant-stasic types of MC, which were prevalent in the majority of patients.

[Atherosclerosis of ascending aorta as a risk factor for neurological complications occurrence in surgical treatment of the ischemic heart disease].

Own experience of the ischemic heart disease (IHD) surgical treatment, combined with the ascending aorta (AA) atherosclerosis, was analyzed. Basing on results of surgical treatment for IHD there were noted mostly informative methods of diagnosis of the AA atherosclerotic affection severity and optimal approaches to surgical treatment of such patients.

Activity of 2-aryl-2-(3-indolyl)acetohydroxamates against drug-resistant cancer cells.

Many types of tumor, including glioma, melanoma, non-small cell lung, esophageal, and head and neck cancer, among others, are intrinsically resistant to apoptosis induction and poorly responsive to current therapies with proapoptotic agents. In addition, tumors often develop multidrug resistance based on the cellular efflux of chemotherapeutic agents. Thus, novel anticancer agents capable of overcoming these intrinsic or developed tumor resistance mechanisms are urgently needed.

Highly efficient modular metal-free synthesis of 3-substituted 2-quinolones.

A modular approach to 3-substituted 2-quinolones via a cascade annulation reaction between 4-nitroketones and hydrazines has been developed.

[Correlation between biomechanical properties of the corneoscleral tunic and stereometric parameters of the optic nerve head in congenital and acquired myopia].

The correlation between biomechanical properties of the corneoscleral tunic and stereometric parameters of the optic nerve head in children and adolescents with congenital and acquired myopia has been studied comparatively. The results showed that in children with high myopia, congenital or acquired, the corneoscleral parameters (scleral echodensity at the equator and the posterior pole, corneoscleral hysteresis, cornea resistance factor, and ocular rigidity coefficient) are lower than those in emmetropes. Moreover, the corneoscleral biomechanical characteristics affect the optic nerve head parameters.

Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones.

3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone.

[The effect of intravenous laser irradiation of blood on the system hemodynamics of patients with chronic obstructive bronchitis exacerbation].

The aim of the study was to evaluate the effects of intravenous laser irradiation of blood (ILIB) on system hemodynamics in patients with chronic obstructive bronchitis (COB) exacerbation. Ninety-seven patients with COB exacerbation were divided into two comparable groups. The 47 patients of the control group received conventional medication, while the 50 patients of the main group received the same therapy plus ILIB, which consisted of 10 everyday 20-min procedures.

[The effects of intravenous laser irradiation of blood on the system hemodynamics of patients with chronic obstructive bronchitis exacerbation].

The aim of the study was to evaluate the effects of intravenous laser irradiation of blood (ILIB) on system hemodynamics in patients with chronic obstructive bronchitis (COB) exacerbation. Ninety-seven patients with COB exacerbation were divided into two comparable groups. The 47 patients of the control group received conventional medication, while the 50 patients of the main group received the same therapy plus ILIB, which consisted of 10 everyday 20-min procedures.

[Regeneration of photoreceptor organs in freshwater planarians at different levels of accumulation of natural methylmercury compounds].

The effects of natural methylmercury compounds on regeneration of photoreceptor organs were studied in three freshwater planarians: Polycelis tenuis, Dugesia lugubris, and D. tigrina. Accumulation of methyl mercury in the planarian body suppressed regeneration of P.

[Laser coagulation in the treatment of different-type retinopathy of prematures].

Laser coagulation of the retina was made in 126 children (238 eyes) with retinopathy of prematures (RP) by an 810 nm diode laser ophthalmocoagulator. The methods of transscleral, transpapillary and combined coagulation were applied. As for children who needed coagulation, 39.

[Platelet aggregatory impairments in chronic obstructive bronchitis and a role of laser therapy in their correction].

A comparative follow-up was made to study platelet aggregatory function in patients with chronic obstructive bronchitis (COB) prior to and following treatment. The patients were divided into study and control groups. In addition to conventional treatment, the patients of the study group received laser therapy as intravenous blood irradiation.