RESUMO
A brown powder and different product packages of "spice-like" herbal incenses were analyzed using a systematic identification approach based on liquid chromatography with diode array detector (HPLC-PDA) and gas chromatography mass spectrometry (GC-MS) with computer based library search against spectral libraries. However, the most predominant compound in the methanolic sample solutions could not be identified. In order to elucidate the chemical structure, a more extensive analysis of the material was initiated using liquid chromatography mass spectrometry (LC-MS), electrospray high resolution mass spectrometry (ESI-HRMS) and 1H, 13C and 19F nuclear magnetic resonance spectroscopy (NMR), which allowed the identification and characterization of the major compound as methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA). The goal of this study is to provide analytical information for the identification of this new tert-leucinate class synthetic cannabinoid by various analytical methods.
RESUMO
Antimicrobial research is increasingly being focused on the problem of resistance and biofilm formation. Hamamelitannin (HAM) was recently identified as an antimicrobial potentiator for conventional antibiotics towards Staphylococcus aureus. This paper describes the synthesis and biological evaluation of novel hamamelitannin analogues with alternative central scaffolds. Via a ligand-based approach, several interesting compounds with improved synthetic accessibility were identified as potentiators for vancomycin in the treatment of MRSA infections.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Desenho de Fármacos , Ácido Gálico/análogos & derivados , Hexoses/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Antibacterianos/síntese química , Antibacterianos/química , Avaliação Pré-Clínica de Medicamentos , Ácido Gálico/síntese química , Ácido Gálico/química , Ácido Gálico/farmacologia , Hexoses/síntese química , Hexoses/química , Ligantes , Testes de Sensibilidade Microbiana , Interface Usuário-ComputadorRESUMO
Staphylococcus aureus is a frequent cause of biofilm-related infections. Bacterial cells within a biofilm are protected from attack by the immune system and conventional antibiotics often fail to penetrate the biofilm matrix. The discovery of hamamelitannin as a potentiator for antibiotics, recently led to the design of a more drug-like lead. In the present study, we want to gain further insight into the structure-activity relationship (S.A.R.) of the 5-position of the molecule, by preparing a library of 21 hamamelitannin analogues.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Ácido Gálico/análogos & derivados , Hexoses/química , Hexoses/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia , Desenho de Fármacos , Ácido Gálico/química , Ácido Gálico/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Percepção de Quorum/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/fisiologia , Relação Estrutura-AtividadeRESUMO
In the recent past sugar-derived cyclopropylamines were proposed as structurally new glycosidase inhibitors. In this Letter we report our efforts in the synthesis of a set of alpha-glucose configured oxabicyclo[4.1.0] heptanes, based on this hypothesis, bearing an amine substituent on the propyl ring and reveal that their inhibitory potential towards a range of mammalian glucosidases is modest.