RESUMO
OBJECTIVE: Mitragynine is the main active compound of Mitragyna speciose (Kratom in Thai). The understanding of mitragynine derivative metabolism in human body is required to develop effective detection techniques in case of drug abuse or establish an appropriate dosage in case of medicinal uses. This in silico study is based upon in vivo results in rat and human by Philipp et al. (J Mass Spectrom 44:1249-1261, 2009). RESULTS: Gas-phase structures of mitragynine, 7-hydroxymitragynine and their metabolites were obtained by quantum chemical method at B3LYP/6-311++G(d,p) level. Results in terms of standard Gibbs energies of reaction for all metabolic pathways are reported with solvation energy from SMD model. We found that 7-hydroxy substitution leads to changes in reactivity in comparison to mitragynine: position 17 is more reactive towards demethylation and conjugation with glucuronic acid and position 9 is less reactive towards conjugation with glucuronic acid. Despite the changes, position 9 is the most reactive for demethylation and position 17 is the most reactive for conjugation with glucuronic acid for both mitragynine and 7-hydroxymitragynine. Our results suggest that 7-hydroxy substitution could lead to different metabolic pathways and raise an important question for further experimental studies of this more potent derivative.
Assuntos
Mitragyna/química , Alcaloides de Triptamina e Secologanina/metabolismo , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Animais , Simulação por Computador , Desmetilação , Ácido Glucurônico/química , Ácido Glucurônico/metabolismo , Humanos , Redes e Vias Metabólicas , Modelos Químicos , Estrutura Molecular , Ratos , Alcaloides de Triptamina e Secologanina/análise , Alcaloides de Triptamina e Secologanina/química , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/prevenção & controleRESUMO
A rhodol-based fluorescent probe has been developed as a selective hydrazine chemosensor using levulinate as a recognition site. The rhodol levulinate probe (RL) demonstrated high selectivity and sensitivity toward hydrazine among other molecules. The chromogenic response of RL solution to hydrazine from colorless to pink could be readily observed by the naked eye, while strong fluorescence emission could be monitored upon excitation at 525â¯nm. The detection process occurred via a ring-opening process of the spirolactone initiated by hydrazinolysis, triggering the fluorescence emission with a 53-fold enhancement. The probe rapidly reacted with hydrazine in aqueous medium with the detection limit of 26â¯nM (0.83â¯ppb), lower than the threshold limit value (TLV) of 10â¯ppb suggested by the U.S. Environmental Protection Agency. Furthermore, RL-impregnated paper strips could detect hydrazine vapor. For biological applicability of RL, its membrane-permeable property led to bioimaging of hydrazine in live HepG2 cells by confocal fluorescence microscopy.
Assuntos
Técnicas Biossensoriais/métodos , Fluorescência , Corantes Fluorescentes/química , Hidrazinas/análise , Imagem Molecular/métodos , Espectrometria de Fluorescência/métodos , Xantonas/química , Células Hep G2 , Humanos , Limite de DetecçãoRESUMO
A rhodol cinnamate fluorescent chemosensor (RC) has been developed for selective detection of hydrazine (N2H4). In aqueous medium, the rhodol-based probe exhibited high selectivity for hydrazine among other molecules. The addition of hydrazine triggered a fluorescence emission with 48-fold enhancement based on hydrazinolysis and a subsequent ring-opening process. The chemical probe also displayed a selective colorimetric response toward N2H4 from colorless solution to pink, readily observed by the naked eye. The detection limit of RC for hydrazine was calculated to be 300nM (9.6ppb). RC is membrane permeable and was successfully demonstrated to detect hydrazine in live HepG2 cells by confocal fluorescence microscopy.
