Neuroepithelial tumor cells were cultured in vitro. The biopsy material was taken from 93 children at removal of the brain tumors during neurosurgical operations. The individual features of the cells ...sensitivity of primary cultures in respect to protocol-approved chemotherapy drugs and changes in the Interleukin-6 (Il-6) level in the culture medium after the application of chemotherapy were established. The initial level of Il-6 exceeded 600.0 pg/ml in the cultural medium with histologically verified pilomyxoid astrocytoma cells, and ranged from 100.0 to 200.0 pg/ml in the medium at cultivation of ganglioneuroblastoma and pilocytic astrocytoma. A decrease in the Il-6 level in the medium culture of primary tumors cells was observed after the application of chemotherapeutic agents on the cells of pilomyxoid astrocytoma, astrocytomas, and pilocytic desmoplastic/nodular medulloblastoma. The production of Il-6 increased after application of cytostatic drugs on the cells of oligoastrocytomas. A decrease in Il-6 level after application of Cisplatin and Methotrexate and a 5-10 fold increase in the level of Il-6 after application of Etoposide, Carboplatin, Cytarabine, and Gemcitabine were registered in the medium with ganglioneuroblastoma. To improve the cytotoxic action of chemotherapeutic agents, the combined application of cytostatics with heterocyclic compounds was carried out. A computer modeling of ligand-protein complexes of carbamide using the Dock 6.4 and USF Chimera program packages was performed with molecular mechanics method. Special attention was drawn to the ability of several isoxazole heterocycles and isothiazolyl to inhibit the tyrosine kinase. It was proved in vitro that the joint application of chemotherapeutic agents and heterocyclic compounds could reduce the concentration of the cytostatic factor by 10 or more times, having maintained the maximum cytotoxic effect. It was assumed that the target amplification of cytotoxic action of chemotherapeutic agents had prospects for reducing toxic side effects of chemotherapy in vivo, which would be carried out only after the preclinical studies.
Molecules in the crystal are joined together by C—H—O hydrogen bonds, forming a three-dimensional network
In the title compound, C
21
H
22
N
2
O
3
S, the 1,2-oxazole ring makes the dihedral angles ...of 9.16 (16) and 87.91 (17)°, respectively, with the toluene and phenyl rings, while they form a dihedral angle of 84.42 (15)° with each other. The C—S—N—C
pr
and C—S—N—C
me
(pr = propene, me = 3-methyl-1,2-oxazole) torsion angles are 86.8 (2) and −100.6 (3) °, respectively. In the crystal, molecules are linked by C—H⋯O hydrogen bonds, generating a three-dimensional network. A Hirshfeld surface analysis was performed to investigate the contributions of the different intermolecular contacts within the supramolecular structure. The major interactions are H⋯H (53.6%), C⋯H/H⋯C (20.8%) and O⋯H/H⋯O (17.7%).
The reaction of 5-arylisoxazolyl- and 4,5-dichloroisothiazolylallylamines with pyromucic acid chlorides (2-furoyl and 5-methyl-2-furoyl chlorides) was studied. The reaction proceeds
via
the initial ...acylation of the allylamine nitrogen atom and the subsequent spontaneous intramolecular Diels–Alder reaction involving the furan ring of intermediate
N
-furoylamides with the formation of a single diastereomer of 3a,6-epoxyisoindol-3-ones.
N
-(4,6-Dimethylpyrimidin-2-yl)-5-phenylisoxazole-3-carboxamide was used as a ligand for obtaining bimetallic boron-containing heterogeneous catalysts Pd–Ni(Co)–B–L (Ni(Co):Pd = 9:1). The obtained ...composites were highly active as catalysts of Suzuki reaction in aqueous media, allowing to develop convenient methods for the synthesis of heterobiaryls containing furyl and thienyl rings.
A reaction sequence involving transformations of 5-(4-methylphenyl)isoxazole and 4,5-dichloroisothiazole derivatives containing an amidoxime group at position 3 allowed to synthesize the respective ...3,5-isoxazolyl(isothiazolyl)-substituted 1,2,4-oxadiazoles. Selective recyclization of 4,5-dichloro-3-(1
Н
-tetrazol-5-yl)isothiazole and 5-(4-methylphenyl)-3-(1
Н
-tetrazol-5-yl)isoxazole gave 2,5-isoxazolyl-(isothiazolyl)-substituted 1,3,4-oxadiazoles. The obtained compounds combining three azole heterocycles in one molecule formed palladium complexes that showed high catalytic activity in Suzuki reactions in aqueous and aqueous alcohol media. The bimetallic reusable Pd/Fe catalyst obtained from palladium polyazole complex retained high catalytic activity after five uses.
2-Mercapto-1,3,4-triazoles and 2-amino-1,3,4-thiadiazoles were synthesized by successive transformations of 5-arylisoxazole- and 4,5-dichloroisothiazole-3-carboxylic acids and their derivatives. The ...amino group of 5-(4,5-dichloroisothiazol-3-yl)-1,3,4-thiadiazol-2-amine was acylated with 5-phenylisoxazole-3-carboxylic acid chloride. Simple approaches to the preparation of previously unknown heterocyclic assemblies containing two or three azole rings with a high potential for biological activity are described.
By alkylation of vanillin with 4,5-dichloro-3-chloromethylisothiazole the corresponding ether was synthesized. The latter was then reacted with p-toluidine to afford the corresponding azomethine. ...During the bioassays of synthesized isothiazolic derivatives of vanillin in mixtures with insecticides (imidacloprid and α-cypermethrin) a strong synergetic effect was observed.
The reaction of 4-substituted anilines with 3,4,4-trichloro-1,1-bis(3,5-dimethyl-1
H
-pyrazol-1-yl)-2-nitrobuta-1,3-dienes led to 1-arylamino-3,4,4-trichloro-1-(3,5-dimethyl-1
H
...-pyrazol-1-yl)-2-nitrobuta-1,3-dienes, which under the action of 2-aminopyridines underwent heterocyclization to the corresponding 2-arylamino-substituted 4-(dichloromethylidene)-3-nitro-4
H
-pyrido1,2-
a
pyrimidines. The molecular structure of 4
H
-pyrido1,2-
a
pyrimidine containing the (4-ethoxyphenyl)amine substituent at position 2 was determined by X-ray structural analysis.
It was found that the reaction of 5-arylfurfurilamines with maleic anhydride leads to the formation of 6-aryl-3a,6-epoxyisoindole-7-carboxylic acids (the cyclic form), which in solution are in ...dynamic equilibrium with
N
-furfurylmaleinamides (the open form). During the esterification of these tautomeric mixtures with methanol in the presence of a catalytic amount of sulfuric acid, methyl esters of 5-aryl-7a-hydroxy-7-methoxy-3-oxo-2,3,3a,4,7,7a-hexahydro-1
H
-isoindole-4-carboxylic acids, unexpected cleavage products of the 3a,6-oxo bridge of the cyclic form, are formed diastereospecifically. The structure of the obtained products was confirmed by X-ray structural analysis.
PDF
