Dissertation/ Thesis
Avaliação de novos compostos sobre a atividade de colinesterases em modelos in silico e in vitro ; Evaluation of new compounds on cholinesterases activity in models in silico and in vitro
| العنوان: | Avaliação de novos compostos sobre a atividade de colinesterases em modelos in silico e in vitro ; Evaluation of new compounds on cholinesterases activity in models in silico and in vitro |
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| المؤلفون: | Lugokenski, Thiago Henrique |
| المساهمون: | Soares, Félix Alexandre Antunes, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769181A8, Monserrat, José María, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769169H6, Franco, Jeferson Luis, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705814T8, Schetinger, Maria Rosa Chitolina, Loro, Vania Lucia, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4796333D7 |
| بيانات النشر: | Universidade Federal de Santa Maria BR Bioquímica UFSM Bioquímica Toxicológica |
| سنة النشر: | 2012 |
| المجموعة: | Manancial - Repositório Digital da UFSM (Universidade Federal de Santa Maria) |
| مصطلحات موضوعية: | Acetilcolinesterase, Organofosforados, Metamidofós, Oximas, Modelos computacionais, Acetylcholinesterase, Organophosphorus, Methamidophos, Oximes, Computational models, CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
| الوصف: | The enzyme acetylcholinesterase (EC 3.1.1.7, AChE) is responsible to terminate acetylcholine activity in the terminal nervous junctions with its effector organs or post-synaptic sites. The activity of this enzyme could be inhibited by organophosphorus (OP) compounds, and this inactivation leads to an accumulation of acetylcholine in the cholinergic receptors, leading to a cholinergic crisis that may result in death. In this way, the OP compound methamidophos has been related to its broad use in various agriculture cultures in Brazil, with high intoxication rate. Actually, the only compounds able to revert the AChE inhibition by OP, are the oxime, such compounds may reactive the enzyme activity due its high nuclephilic power, attacking the phosphoryl group of the inhibited enzyme and displacing it. However, such compounds show toxic effects, and its use is limited by the high specificity, with each oxime acting only in the reactivation of AChE induced by specific OP coumponds. These limitations raise the need of development of new compounds with AChE reactivator potency, with minor side effects. In this way, have been utilized a series of computational tools (in silico models), with the aim of understand the interaction occurring at a molecular level and, so, rationalize the new compounds development. Thus, the aim of this thesis is to evaluate the activity of three new compounds in reactivate the AChE inhibited by methamidophos, in comparison with two others oximes used in clinical (obidoxime and pralidoxime), both in in silico and in vitro models. Our work demonstrate that the newly synthesized compounds are able to reactivate human erythrocyte AChE, however less efficiently than pralidoxime and obidoxime, and reactivate human plasma butyrylcholinesterase (BChE), where the classical oximes failed. We also show that pralidoxime, which obtained the best reactivation constant among all tested compounds, attack the phosphorus-oxygen moiety (formed between the methamidophos and the AChE catalytic triad residue ... |
| نوع الوثيقة: | thesis |
| وصف الملف: | application/pdf |
| اللغة: | Portuguese |
| Relation: | LUGOKENSKI, Thiago Henrique. EVALUATION OF NEW COMPOUNDS ON CHOLINESTERASES ACTIVITY IN MODELS IN SILICO AND IN VITRO. 2012. 107 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012.; http://repositorio.ufsm.br/handle/1/4457 |
| الاتاحة: | http://repositorio.ufsm.br/handle/1/4457 |
| Rights: | Acesso Aberto |
| رقم الانضمام: | edsbas.9660934B |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |