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1.
J Nat Prod ; 80(3): 684-691, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28128950

RESUMO

HeLa cell-based cytological profiling (CP) was applied to an extract library of marine sediment-derived actinomycetes to discover new cytotoxic secondary metabolites. Among the hit strains, Streptomyces sp. CP26-58 was selected for further investigation to identify its cytotoxic metabolites. CP revealed that the known ionophore tetronasin (1) was responsible for the cytotoxic effect found in the extract. Furthermore, three naphthoquinone meroterpenoids, naphthablin A (2) and two new derivatives designated as naphthablins B (3) and C (4), were isolated from other cytotoxic fractions. The structures of the new compounds were elucidated based on analysis of their HRESIMS and comprehensive NMR data. The absolute configurations of the new compounds were deduced by simulating ECD spectra and calculating potential energies for the model compounds using density function theory (DFT) calculations. Compound 1 showed a significant cytotoxic effect against HeLa cells with an IC50 value of 0.23 µM, and CP successfully clustered 1 with calcium ionophores.


Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Sedimentos Geológicos/química , Streptomyces/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Antibacterianos/farmacologia , Antineoplásicos/química , Células HeLa , Humanos , Concentração Inibidora 50 , Biologia Marinha , Estrutura Molecular , Naftoquinonas , Ressonância Magnética Nuclear Biomolecular , Terpenos/química
2.
Forensic Sci Int ; 283: e13-e17, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29254806

RESUMO

Fatalities from emerging synthetic opioids have continued to reach new epidemic proportions throughout the world in recent years. Due to the sparsity of research in new opioid analogs, commonly observed lethal concentrations and their distribution following death have yet to be well documented. The prevalence of furanyl fentanyl in postmortem casework contributes to the opioid related deaths that are amongst half of drug-induced fatalities in the United States. In this case study, a 23-year-old man was found dead in San Francisco following the ingestion of blue pills imitating oxycodone. Initial toxicology screening did not detect oxycodone in blood. However, a positive fentanyl immunoassay result was obtained and analysis of the pills collected at the scene showed the presence of furanyl fentanyl. Analysis of postmortem samples revealed concentrations of furanyl fentanyl at 1.9ng/mL in peripheral blood, 2.8ng/mL in cardiac blood, and ∼55,000ng in gastric contents. Metabolite 4-anilino-N-phenethyl-piperidine (4-ANPP) was also confirmed at 4.3ng/mL and 5.8ng/mL in peripheral blood and cardiac blood, respectively. Trace amounts of both analytes were detected in urine and the vitreous humor. Liver 4-ANPP concentrations of >40ng/g were also detected. This case study of acute furanyl fentanyl overdose in a young male thought to be using oxycodone highlights illicit drug users are often subject to unknown drug entities. The toxicological analysis provides preliminary information of the distribution of furanyl fentanyl and its metabolite in a range of postmortem specimens and collection sites.


Assuntos
Analgésicos Opioides/análise , Drogas Desenhadas/análise , Fentanila/análogos & derivados , Furanos/análise , Conteúdo Gastrointestinal/química , Corpo Vítreo/química , Overdose de Drogas , Fentanila/análise , Humanos , Masculino , Adulto Jovem
3.
Astrobiology ; 13(6): 515-20, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23746165

RESUMO

Results from the Viking biology experiments indicate the presence of reactive oxidants in martian soils that have previously been attributed to peroxide and superoxide. Instruments on the Mars Phoenix Lander and the Mars Science Laboratory detected perchlorate in martian soil, which is nonreactive under the conditions of the Viking biology experiments. We show that calcium perchlorate exposed to gamma rays decomposes in a CO2 atmosphere to form hypochlorite (ClO(-)), trapped oxygen (O2), and chlorine dioxide (ClO2). Our results show that the release of trapped O2 (g) from radiation-damaged perchlorate salts and the reaction of ClO(-) with amino acids that were added to the martian soils can explain the results of the Viking biology experiments. We conclude that neither hydrogen peroxide nor superoxide is required to explain the results of the Viking biology experiments.


Assuntos
Marte , Percloratos/química , Radiometria , Solo
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