Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros

Base de dados
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Bioorg Chem ; 129: 106163, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36137313

RESUMO

Ionotropic glutamate receptors are ligand-gated ion channels found in most excitatory synapses in the brain that allow for rapid information transfer. Due to their quick excitatory processes, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate (AMPA) receptors have been linked to various neurodegenerative disorders, including epilepsy and Parkinson's disease. It has been critical to develop new neuroprotective compounds that inhibit AMPA-sensitive glutamate-controlled channels allosterically, and many classes of AMPA receptor-inhibiting compounds have been synthesized and evaluated. The current study focuses on thirteen 2-oxo-3H-benzoxazole derivatives (COBs) as potential AMPA receptor modulators. The whole-cell patch-clamp technique was used to assess the effects of COBs on AMPA receptor subunits (i.e., GluA1, GluA2, GluA1/2, and GluA2/3) amplitudes in the human embryonic kidney (HEK293) cells and the rates of desensitization and deactivation before and after COBs delivery. According to our findings, the COBs bind AMPA receptors allosterically and alter AMPAR characteristics in various ways. COB-1, COB-2, and COB-13 were the most effective in decreasing AMPAR currents by around 10-12 folds compared to the other COBs. Furthermore, the COBs significantly impacted AMPA receptor deactivation and desensitization rates. Of the examined homomeric and heteromeric AMPAR subunits, GluA2 was the most impacted. COB compounds appear to be a viable candidate for future study and development in regulating neurological diseases involving AMPA receptors.


Assuntos
Benzoxazóis , Receptores de AMPA , Humanos , Receptores de AMPA/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia , Benzoxazóis/farmacologia , Células HEK293 , Ácido Glutâmico
2.
Arh Hig Rada Toksikol ; 70(3): 160-172, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32597128

RESUMO

The entire world is looking for effective cancer therapies whose benefits would outweigh their toxicity. One way to reduce resistance to chemotherapy and its adverse effects is the so called targeted therapy, which targets specific molecules ("molecular targets") that play a critical role in cancer growth, progression, and metastasis. One such specific target are microtubules. In this review we address the current knowledge about microtubule-targeting agents or drugs (MTAs/MTDs) used in cancer therapy from their synthesis to toxicities. Synthetic and natural MTAs exhibit antitumor activity, and preclinical and clinical studies have shown that their anticancer effectiveness is higher than that of traditional drug therapies. Furthermore, MTAs involve a lower risk of adverse effects such as neurotoxicity and haemotoxicity. Several new generation MTAs are currently being evaluated for clinical use. This review brings updated information on the benefits of MTAs, therapeutic approaches, advantages, and challenges in their research.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Microtúbulos/efeitos dos fármacos , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
3.
J Pharm Pharmacol ; 70(12): 1619-1629, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30198567

RESUMO

OBJECTIVES: Pyrazole derivatives are pharmacologically powerful agents pointing at new horizons in the development of anticancer therapies. In this study, anticarcinogenic potential of a series of pyrazole-acrylamide derivatives has been investigated in mesothelial, malignant mesothelioma and lung cancer cell lines. METHODS: The effect of compounds on the viability of cells and the distribution of cell cycle were examined through MTS assay and PI staining, respectively. Apoptosis was evaluated via caspase-3 enzymatic assay and AO/EB staining. Proteins involved in proliferation, survival and apoptosis were analysed by immunoblotting. KEY FINDINGS: Twelve compounds of 21 (4a-4v) reduced the viability of cells but, only the subset of five (4f, 4i, 4j, 4k and 4v) induced the caspase-3 activity. Among five, only one compound (4k) significantly suppressed phosphorylation and expression of ERK1/2 and AKT proteins in 24 h. Exposing cancer cells to successive concentrations of 4k gave rise to dose- and time-dependent G2/M phase arrest and apoptosis. CONCLUSIONS: 4k has revealed its potent antiproliferative activity by decreasing viability and inhibiting proliferation and survival signals of cancer cells. Moreover, 4k has exposed cytostatic and apoptotic effect especially, on cancer cells. Therefore, it may be necessary to examine the biological actions of 4k in vivo as well.


Assuntos
Acrilamida/farmacologia , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Pirazóis/farmacologia , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Immunoblotting , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Sinalização das MAP Quinases , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA