engleski

Theoretical study of psychoactive drugs. 1. Conformational analysis of nitrazepam by semiempirical quantum chemical methods

Objectives: Nitrazepam is known as anticonvulsant and hypnotic drug. Benzodiazepines have been recognized in the literature and clinical practice for their capacity to cause mental and behavioral abnormalities. Structural nitrazepam features can be related to the toxicity of this drug. Methods: In this study the structure of nitrazepam was studied by molecular mechanics using the MM2 force field and the AM1 and PM3 quantum chemical methods. Results: Several conformations were generated by molecular mechanics calculations and the low energy conformations thus obtained were further minimized by the semiempirical AM1 and PM3 approaches. Bond lengths and angles of the minimum energy structures were then compared to the experimental X-ray crystallography data by statistical analysis. Consistent results were obtained by the semiempirical molecular orbital AM1 method. Conclusions: Nitrazepam structure obtained by the AM1 method is in good agreement with the crystallographic data and can be further used in structure-toxicity studies.

conformation; drug; molecular mechanics; nitrazepam; toxicity

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