Metabolite

Letrozole is an aromatase inhibitor, used to treat postmenopausal women with hormone receptor‐positive or unknown advanced breast cancer. It is prohibited in sport because it is used together with androgen anabolizing steroids to avoid their adverse effects. In the case of an adverse analytical finding, it may be important to distinguish between repetitive use due to voluntary administration and occasional use, possibly due to involuntary intake. With the objective to identify the dose capable of producing a positive hair test, and to apply these results to the scenarios of inadvertent letrozole ingestion by an athlete, this study investigates the urinary excretion and incorporation into hair of single doses of letrozole. Seven subjects were recruited for an excretion study of letrozole and its metabolite bis(4‐cyanophenyl) methanol (M1) in urine, after the consumption of 0.62 mg, 1.25 mg, and 2.5 mg of letrozole, and to investigate the incorporation in hair after ingestion of 0.62 ...

Streptomyces hygroscopicus Hygroscopicus, a member of family of Actinomycetes produces eponemycin a proteasome inhibitor that can inhibit Ubiquitin-Proteasome System (UPS) function in eukaryotic cell. Previous study showed that coronamycin, an active substrate isolated from Streptomyces sp. can act as anti-plasmodial, antibacterial, and antifungal, however the research did not show the mechanism of coronamycin in inhibiting the growth of Plasmodium. This research was done to reveal if eponemycin that is contained in metabolite extract of S. hygroscopicus can inhibit UPS function of Plasmodium berghei. This study was an experimental study using P. berghei infected Balb/C mice as malaria model. Samples were divided into 1 control group (group infected with P. berghei without treatment) and 3 treatment groups (mice infected with P. berghei and treated intra-peritoneal with metabolite extract of S. hygroscopicus dose 130 μg/kgBW, 580 μg/kgBW, and 2600 μg/kgBW for 5 days). The degree of ...

Genistein is a naturally occurring phytoestrogen isoflavone and is the active drug ingredient in BIO 300, a radiation countermeasure under advanced development for acute radiation syndrome (H-ARS) and for the delayed effects of acute radiation exposure (DEARE). Here we have assessed the pharmacokinetics (PK) and safety of BIO 300 in the nonhuman primate (NHP). In addition, we analyzed serum samples from animals receiving a single dose of BIO 300 for global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS). We present a comparison of how either intramuscularly (im) or orally (po) administered BIO 300 changed the metabolomic profile. We observed transient alterations in phenylalanine, tyrosine, glycerophosphocholine, and glycerophosphoserine which reverted back to near-normal levels 7 days after drug administration. We found a significant overlap in the metabolite profile changes induced by each route of admi...

Metabolic footprinting offers a relatively easy approach to exploit the potentials of metabolomics for phenotypic characterization of microbial cells. To capture the highly dynamic nature of metabolites, we propose the use of dynamic metabolic footprinting instead of the traditional method which relies on analysis at a single time point. Using direct infusion-mass spectrometry (DI-MS), we could observe the dynamic metabolic footprinting in yeast S. cerevisiae BY4709 (wild type) cultured on 3 different C-sources (glucose, glycerol, and ethanol) and sampled along 10 time points with 5 biological replicates. In order to analyze the dynamic mass spectrometry data, we developed the novel analysis methods that allow us to perform correlation analysis to identify metabolites that significantly correlate over time during growth on the different carbon sources. Both positive and negative electrospray ionization (ESI) modes were performed to obtain the complete information about the metabolit...

In present study, the combinable approach of freezing and thawing and aqueous two-phase partitioning system was designed for simple, rapid and cost friendly extraction and purification of Spirulina plantesis phycocyanin. From cell extract, C-PC was purified 1.38-fold 51.35% recovery by ammonium sulphate fractionation then PEG3000/KH2PO4/K2HPO4 system at pH 7. Contrary to expectations, increasing neutral salt concentrations resulted in decreased C-PC recovery, deviating from the typical enhancement of biomolecular partitioning performance in aqueous two-phase systems. The C-PC showed remarkable in vitro antioxidant and radical-scavenging activity. 200 µg/mL C-PC, performed a maximum absorbance by phosphomolybdenum and ferric ion reducing assay, 0.55 and 0.45, respectively. H2O2 scavenging activity was defined as 93.67%. Notably, modified C-PC (m-C-PC) exhibited improved photostability under yellow light exposure compared to unmodified C-PC, showcasing a 1.064-fold enhancement after 540 minutes. However, m-C-PC showed increased susceptibility to white light, UV-A and UV-B irradiation, suggesting a failure to enhance stability under these conditions.

Difficulties inherent in working with anaerobic microorganisms and mixed cultures have hampered efforts to detect and identify metabolites of anaerobic degradation of monoaromatic compounds. Isotope-trapping experiments and analysis using a high-performance liquid chromatograph equipped with a flow-through radioactivity detector were used to detect very low concentrations of metabolites. Data obtained by this method suggest that toluene was degraded via methyl hydroxylation by a mixed methanogenic culture.

Realizing an increasing need for a novel antibiotic, this study was carried out to screen antibacterial metabolites producing actinomycetes from 15 soil samples collected from Taplejung. Antibacterial metabolites producing actinomycetes were confirmed by primary screening and secondary screening. Macroscopic, microscopic, and biochemical characteristics were used for presumptive identification of probable actinomycetes genera. The potential isolate was cultured in starch casein broth for production of possible antibacterial compound. The antibacterial compound was extracted from fermented broth using organic solvents like ethyl acetate, n-butanol, chloroform, dichloromethane, and methanol. Among 24 isolates, only one (T18) showed antibacterial activity against both Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli, Salmonella Typhi and Pseudomonas aeruginosa) test-bacteria. The isolate was considered as Streptomyces spp based on microsco...

Metabolite identification is a crucial part of the drug discovery process. LC–MS/MS-based metabolite identification has gained widespread use, but the data acquired by the LC–MS/MS instrument is complex, and thus the interpretation of data becomes troublesome. Fortunately, advancements in data mining techniques have simplified the process of data interpretation with improved mass accuracy and provide a potentially selective, sensitive, accurate and comprehensive way for metabolite identification. In this review, we have discussed the targeted (extracted ion chromatogram, mass defect filter, product ion filter, neutral loss filter and isotope pattern filter) and untargeted (control sample comparison, background subtraction and metabolomic approaches) post-acquisition data mining techniques, which facilitate the drug metabolite identification. We have also discussed the importance of integrated data mining strategy.

Accurate blood-based biomarkers of Alzheimer's disease (AD) could constitute simple, inexpensive, and non-invasive tools for the early diagnosis and treatment of this devastating neurodegenerative disease. We sought to develop a robust AD biomarker panel by identifying alterations in plasma metabolites that persist throughout the continuum of AD pathophysiology. Using a multicenter, cross-sectional study design, we based our analysis on metabolites whose levels were altered both in AD patients and in patients with amnestic mild cognitive impairment (aMCI), the earliest identifiable stage of AD. UPLC coupled to mass spectrometry was used to independently compare the levels of 495 plasma metabolites in aMCI (n = 58) and AD (n = 100) patients with those of normal cognition controls (NC, n = 93). Metabolite alterations common to both aMCI and AD patients were used to generate a logistic regression model that accurately distinguished AD from NC patients. The final panel consisted of ...