Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Int J Mol Sci ; 24(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37511087

RESUMO

Prostate cancer is the second most common cancer among men. We designed and synthesized new ligands targeting prostate-specific membrane antigen and suitable for bimodal conjugates with diagnostic and therapeutic agents. In vitro studies of the affinity of the synthesized compounds to the protein target have been carried out. Based on these ligands, a series of bimodal conjugates with a combination of different mitosis inhibitors and antiandrogenic drugs were synthesized. The cytotoxicity of the compounds obtained in vitro was investigated on three different cell lines. The efficacy of the two obtained conjugates was evaluated in vivo in xenograft models of prostate cancer. These compounds have been shown to be highly effective in inhibiting the growth of PSMA-expressing tumors.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Masculino , Humanos , Antagonistas de Androgênios/uso terapêutico , Citotoxinas/uso terapêutico , Próstata/patologia , Ligantes , Linhagem Celular Tumoral , Glutamato Carboxipeptidase II/metabolismo , Antígenos de Superfície/metabolismo , Neoplasias da Próstata/metabolismo
2.
Int J Mol Sci ; 24(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36902468

RESUMO

Novel hydantion and thiohydantoin-based spiro-compounds were prepared via theDiels-Alder reactions between 5-methylidene-hydantoins or 5-methylidene-2-thiohydantoins and 1,3-dienes (cyclopentadiene, cyclohexadiene, 2,3-dimethylbutadiene, isoprene). It was shown that the cycloaddition reactions proceed regioselectively and stereoselectively with the formation of exo-isomers in the reactions with cyclic dienes andthe less sterically hindered products in the reactions with isoprene. Reactions of methylideneimidazolones with cyclopentadiene proceed viaco-heating the reactants; reactions with cyclohexadiene, 2,3-dimethylbutadiene, and isoprene require catalysis by Lewis acids. It was demonstrated that ZnI2 is an effective catalyst in the Diels-Alder reactions of methylidenethiohydantoins with non-activated dienes. The possibility of alkylation and acylation of the obtained spiro-hydantoinsat the N(1)nitrogen atoms with PhCH2Cl or Boc2O and the alkylation of the spiro-thiohydantoinsat the S atoms with MeI or PhCH2Cl in high yields have been demonstrated. The preparativetransformation of spiro-thiohydantoins into corresponding spiro-hydantoinsin mild conditions by treating with 35% aqueous H2O2 or nitrile oxide has been carried out. The obtained compounds show moderate cytotoxicity in the MTT test on MCF7, A549, HEK293T, and VA13 cell lines. Some of the tested compounds demonstrated some antibacterial effect against Escherichia coli (E. coli) BW25113 DTC-pDualrep2 but were almost inactive against E. coli BW25113 LPTD-pDualrep2.


Assuntos
Hidantoínas , Humanos , Tioidantoínas , Reação de Cicloadição , Escherichia coli , Células HEK293 , Peróxido de Hidrogênio , Ciclopentanos
3.
Int J Mol Sci ; 23(12)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35743110

RESUMO

In this work, we present the first synthesis of dispirooxindole-ß-lactams employing optimized methodology of one-pot Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with ß-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against E. coli strain LPTD.


Assuntos
Iminas , beta-Lactamas , Reação de Cicloadição , Escherichia coli , Etilenos , Células HEK293 , Humanos , Cetonas , beta-Lactamas/farmacologia
4.
R Soc Open Sci ; 9(3): 211967, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35291328

RESUMO

A synthesis of dispiro derivatives from 5-methylidene-2-chalcogenimidazolones and azomethine ylides generated from isatins and N-substituted α-amino acids has been developed.

5.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807662

RESUMO

A regio- and diastereoselective synthesis of two types of dispiro derivatives of 2-selenoxoimidazolidin-4-ones, differing in the position of the nitrogen atom in the central pyrrolidine ring of the spiro-fused system-namely, 2-selenoxodispiro[imidazolidine-4,3'-pyrrolidine-2',3″-indoline]-2″,5-diones (5a-h) and 2-senenoxodispiro[imidazolidine-4,3'-pyrrolidine-4',3″-indoline]-2″,5-diones (6a-m)-were developed based on a 1,3-dipolar cycloaddition of azomethine ylides generated from isatin and sarcosine or formaldehyde and sarcosine to 5-arylidene or 5-indolidene-2-selenoxo-tetrahydro-4H-imidazole-4-ones. Selenium-containing dispiro indolinones generally exhibit cytotoxic activity near to the activity of the corresponding oxygen and sulfur-containing derivatives. Compounds 5b, 5c, and 5e demonstrated considerable in vitro cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) test (concentration of compounds that caused 50% death of cells (CC50) 7.6-8.7 µM) against the A549 cancer cell line with the VA13/A549 selectivity index 5.2-6.9; some compounds (5 and 6) increased the level of intracellular reactive oxygen species (ROS) in the experiment on A549 and PC3 cells using platinized carbon nanoelectrode. The tests for p53 activation for compounds 5 and 6 on the transcriptional reporter suggest that the investigated compounds can only have an indirect p53-dependent mechanism of action. For the compounds 5b, 6b, and 6l, the ROS generation may be one of the significant mechanisms of their cytotoxic action.


Assuntos
Citotoxinas , Neoplasias/tratamento farmacológico , Pirrolidinas , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Células PC-3 , Pirrolidinas/síntese química , Pirrolidinas/química , Pirrolidinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA