RESUMO
Primary tumor cells often spread to other organs by metastasis. Despite of it, primary tumor cells break their surrounding extra cellular matrix (ECM) proteins and reach the destination organ by the process of intravasation and extravasation. Metastasized tumor cells induce the process of angiogenesis, this highly regulated process involves several ECM proteins. However, integrins are primarily involved in the blood vessel growth and repair. Therefore, integrins are promising angiogenesis targets. Integrins are receptors on cell surface, involved in signal transduction and attachments in extra cellular matrix (ECM). IntegrinαVß3 and αVß5 are implicated in tumor angiogenesis, metastasis, inflammation and bone resorption. The crystal structure of integrinαvß5 is not available in protein structural databases, therefore; molecular model of integrinß5 structure was prepared and stereo chemical model quality was checked. Integrin ß5 active sites were identified based on insilico analysis tools. Further, molecular level interactions between integrinß5 and ECM proteins were predicted. In the present study ECM proteins such as focal adhesion kinase 1 (FAK1), annexin A5 and P21 activated kinase 4 (PAK4) were considered for protein-protein docking, to understand inter molecular interactions. The predicted model is conceived to be stereo chemically good and can be used for molecular interaction studies of angiogenic inhibitors.
Assuntos
Domínio Catalítico , Cadeias beta de Integrinas/química , Modelos Moleculares , Neoplasias/metabolismo , Anexina A5/química , Sítios de Ligação , Simulação por Computador , Matriz Extracelular/química , Quinase 1 de Adesão Focal/química , Quinase 1 de Adesão Focal/metabolismo , Humanos , Cadeias beta de Integrinas/genética , Cadeias beta de Integrinas/metabolismo , Simulação de Acoplamento Molecular , Metástase Neoplásica , Neoplasias/química , Neovascularização Patológica/metabolismo , Ligação Proteica , Quinases Ativadas por p21/química , Quinases Ativadas por p21/metabolismoRESUMO
A thorough survey of the literature has revealed that indole derivatives have shown various central nervous system activities. This study aims to evaluate the antidepressant activity of the newly synthesized dialkyl- [2-(1-oxa-3,4,9-triaza-fluoren-2-yl-methoxy)ethyl] amines and their effect on biogenic amines. In this study, the synthesized compounds were assessed by in-vivo antidepressant models, by forced swim test and tail suspension test in mice and effect of synthesized compounds on biogenic amines in brain in a chronic unpredictable stress model. The test compounds have demonstrated significant (P < 0.05) reduced immobility duration in mice when compared with the control group animals. The reduced immobility displayed by mice indicates potential antidepressant activity. In this study, chronic unpredictable stress led to decreased monoamine levels in the cortex and hippocampus regions of the brain. With chronic administration of the investigated compounds there is an increased in monoamines in the brain, in the chronic unpredictable stress model. Decreased levels of monoamines induced by the chronic unpredictable stress induced model of depression, were normalized by treatment with the test compounds, which indicates potential antidepressant activity.
