Structure and toxicity of clozapine and olanzapine on agranulocytosis
| Autor: | Cristiane Socorro Ferraz Maia, Albérico B. F. da Silva, Ednilsom Orestes, Gláucio R. Nagurniak, Carlos A. L. Barros, Luana Melo Diogo de Queiroz, Rosivaldo S. Borges |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Olanzapine Hydrogen Stereochemistry Radical Organic Chemistry QUÍMICA QUÂNTICA chemistry.chemical_element 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Diazepine chemistry Computational chemistry Toxicity medicine Reactivity (chemistry) Density functional theory General Pharmacology Toxicology and Pharmaceutics Clozapine medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1554-8120 1054-2523 |
| Popis: | The structure and toxicity relationship of the dibenzo-1,4-diazepine derivatives has been investigated using quantum chemical calculations at the density functional theory level/B3LYP with the 6-311G(d,p) basis sets by electron or hydrogen transfer calculations as model for the reaction prediction between the derivatives and the free radical species on agranulocytosis. Our results show that the abstraction of an electron or hydrogen from the amino group of the olanzapine is more favored than clozapine. The spin density calculations performed for the radicals formed clarify that olanzapine is more stable than clozapine. These results support that the highest toxicity of the 1,4-dibenzodiazepine compounds on agranulocytosis can be related with a high reactivity of diazepine ring in agreement to experimental results. The toxicity of dibenzo-1,4-diazepine derivatives is more related to hydrogen than electron transfers. |
| Databáze: | OpenAIRE |
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