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| A. Ciências Exatas e da Terra - 4. Química - 1. Físico-Química | ||
| A CHEMOMETRIC STUDY OF PSYCHOACTIVE CANNABINOID COMPOUNDS | ||
| Albérico B.F. da Silva 1 (alberico@iqsc.usp.br) e Káthia M. Honório 2 | ||
| (1. Instituto de Química de São Carlos, Universidade de São Paulo; 2. Instituto de Física de São Carlos, Universidade de São Paulo) | ||
| INTRODUÇÃO:
The plant Cannabis sativa L. has been used by man for centuries for eating, medicinal practices and religious rituals. Nowadays, there are many valuable discoveries regarding Cannabis, but many myths and uncertainties still persist. Due to the great interest in the effects caused by the compounds extracted from the Cannabis, several studies have been carried out with the aim to better understand the relationship between the chemical structure and the biological activity of cannabinoid compounds. |
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| METODOLOGIA:
Several molecular properties are calculated for a set of 26 cannabinoid compounds with the goal of connecting the psychoactivity of the compounds with the calculated properties. For this purpose we used quantum chemical (the AM1 semi-empirical method) and chemometric methods. The AM1 method was employed to calculate the set of quantum chemical molecular properties and the chemometric methods were employed with the aim to select the most relevant properties to be correlated with the psychoactivity. The chemometric methods used were Principal Component Analysis (PCA), Hierarchical Clusters Analysis (HCA) and the K-Nearest Neighbor (KNN) method. |
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| RESULTADOS:
The chemometric analysis showed that an electronic property (energy of LUMO), a hydrophobic property (log P), a steric property (volume of the substituent at the C4 position) and a topological property (Lovasz-Pelikan index) were the most important variables for the separation between the psychoactive and psychoinactive compounds. In order to validate our PCA, HCA and KNN results, 8 new cannabinoid compounds (with known psychoactivity) were used in a prediction study and were correctly classified by the methods used in this work, indicating that our PCA, HCA and KNN models are able to give reliable information on the psychoactivity of cannabinoid compounds. |
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| CONCLUSÕES:
According to our chemometry study, the interaction between the cannabinoid compounds studied and the biological receptor can occur due to electronic, hydrophobic, steric and topological features of the compounds. Thus, in order to design new psychoinactive cannabinoids it is necessary that the candidate molecule presents high values for VC4 and LP1 and low values for ELUMO and Log P. |
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| Instituição de fomento: CNPq/FAPESP | ||
| Palavras-chave: Cannabinoid compounds; Psychoactivity; Quantum chemical and chemometric methods. | ||
| Anais da 57ª Reunião Anual da SBPC - Fortaleza, CE - Julho/2005 |