Development of new HPLC method for identification of metabolic degradation of N-pyrrolylhydrazide hydrazones with determined MAO- B activity in cellular cultures

In this research, a new rapid PR- HPLC method was developed for the determination of metabolites in isolated rat hapatocytes. The chromatographic parameters, including the stationary and mobile phases, outlet pressure, temperature and flow rate, were optimized. The method identified two initial from the synthesis molecules in higher concentration and one new unidentified structure as products of the hepatocytic processing of the evaluated analyte. The results identified as first step of metabolism the hydrolysis of the hydrazone group. Further investigations should be aimed into determining the next metabolic transformations, predicted by the in silico application of the web server SMARTCyp.

Profiling of co-metabolic degradation of tetracycline by the bio-cathode in microbial fuel cells

In this paper, a system of tetracycline (TEC) degradation by the bio-cathode in a microbial fuel cell (MFC) was constructed.

Potential Application of Algae in Biodegradation of Phenol: A Review and Bibliometric Study

One of the most severe environmental issues affecting the sustainable growth of human society is water pollution. Phenolic compounds are toxic, hazardous and carcinogenic to humans and animals even at low concentrations. Thus, it is compulsory to remove the compounds from polluted wastewater before being discharged into the ecosystem. Biotechnology has been coping with environmental problems using a broad spectrum of microorganisms and biocatalysts to establish innovative techniques for biodegradation. Biological treatment is preferable as it is cost-effective in removing organic pollutants, including phenol. The advantages and the enzymes involved in the metabolic degradation of phenol render the efficiency of microalgae in the degradation process. The focus of this review is to explore the trends in publication (within the year of 2000–2020) through bibliometric analysis and the mechanisms involved in algae phenol degradation. Current studies and publications on the use of algae in bioremediation have been observed to expand due to environmental problems and the versatility of microalgae. VOSviewer and SciMAT software were used in this review to further analyse the links and interaction of the selected keywords. It was noted that publication is advancing, with China, Spain and the United States dominating the studies with total publications of 36, 28 and 22, respectively. Hence, this review will provide an insight into the trends and potential use of algae in degradation.

Enhanced biodegradation of ciprofloxacin by enrich nitrifying sludge: assessment of removal pathways and microbial responses

Antibiotics are mostly collected by sewage systems, but not completely removed within wastewater treatment plants. Their release to aquatic environment poses great threat to public health. This study evaluated the removal of a widely used fluoroquinolone antibiotic ciprofloxacin in enriched nitrifying culture through a series of experiments by controlling ammonium concentrations and inhibiting functional microorganisms. The removal efficiency of ciprofloxacin at an initial concentration of 50 μg L−1 reached 81.86 ± 3.21% in the presence of ammonium, while only 22.83 ± 8.22% of ciprofloxacin was removed in its absence. The positive linear correlation was found between the ammonia oxidation rate (AOR) and ciprofloxacin biodegradation rate. These jointly confirmed the importance of the AOB-induced cometabolism in ciprofloxacin biodegradation with adsorption and metabolic degradation pathways playing minor roles. The continuous exposure of AOB to ciprofloxacin led to decreases of ammonia monooxygenase (AMO) activities and AOR. The antibacterial effects of ciprofloxacin and its biodegradation products were further evaluated and the results revealed that biodegradation products of ciprofloxacin exhibited less toxicity compared to the parent compound, implying the potential application of cometabolism in alleviation of antimicrobial activity. The findings provided new insights into the AOB-induced cometabolic biodegradation of fluoroquinolone antibiotics.

Unraveling the Bacterial Assisted Degradation Pathway of Morpholine- a Xenobiotic Micropollutant: A Sustainability for Zero Pollution Environment

Biodegradation is the process by which chemicals both natural and xenobiotics are metabolized by microorganisms. Most naturally occurring chemical compounds are biodegradable while xenobiotic may be biodegradable, persistent or recalcitrant. Xenobiotic chemicals, because they are manmade and have developed recently, are present in the environment for comparatively shorter periods of time from its geological presence. This in turn means that the microbial communities present in these environments may not have evolved specific mechanisms for their degradation. Morpholine, a known xenobiotics micropollutant initially believes to be recalcitrant but later prove to be biodegradable by specific set of bacterium species most likely Mycobacterium and Pseudomonas sp in particular. However, the metabolic pathways involved in the successful biodegradation of morpholine stand challenging to establish because of its extreme water solubility and the lack of any chromophore group in morpholine which does not allow easy extraction process. Consequently, no tool for direct estimation of intermediates or metabolites of morpholine has been well reported and only indirect strategies have been developed like presence of microbial growth on intermediates, chemical/analytical assay for intermediate and ammonia measurements to elucidate the degradation pathway for zero pollution environment. In this present study degradation pathway has been ascertained by some selected bacterial isolate for their capacity to degrade morpholine. Based on the said analysis of culture filtrate, it has been revealed that the isolate namely Halobacillus utilizes glycolic route of the metabolic degradation pathway of morpholine and supports the fact that in presence of morpholine, one of two branches of morpholine biodegradation pathway namely ethanolamine and glycolate was was induced while the other branch was inhibited. Whatever the degradation pathway of morpholine exhibited by bacteria, ammonia is the end product of degradation which would be biochemically utilized by isolate.

Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes

Peptide therapeutics offer numerous advantages in the treatment of diseases and disorders of the central nervous system (CNS). However, they are not without limitations, especially in terms of their pharmacokinetics where their metabolic lability and low blood–brain barrier penetration hinder their application. Targeted nanoparticle delivery systems are being tapped for their ability to improve the delivery of therapeutics into the brain non-invasively. We have developed a family of mannosylated glycoliposome delivery systems for targeted drug delivery applications. Herein, we demonstrate via in vivo distribution studies the potential of these glycoliposomes to improve the utility of CNS active therapeutics using dynantin, a potent and selective dynorphin peptide analogue antagonist of the kappa opioid receptor (KOR). Glycoliposomal entrapment protected dynantin against known rapid metabolic degradation and ultimately improved brain levels of the peptide by approximately 3–3.5-fold. Moreover, we linked this improved brain delivery with improved KOR antagonist activity by way of an approximately 30–40% positive modulation of striatal dopamine levels 20 min after intranasal administration. Overall, the results clearly highlight the potential of our glycoliposomes as a targeted delivery system for therapeutic agents of the CNS.

Improved Tumor-Targeting with Peptidomimetic Analogs of Minigastrin 177Lu-PP-F11N

The cholecystokinin-2 receptor (CCK2R) is an attractive target in nuclear medicine due to its overexpression by different tumors. Several radiolabeled peptidic ligands targeting the CCK2R have been investigated in the past; however, their low stability against proteases can limit their uptake in tumors and metastases. Substitution of single or multiple amide bonds with metabolically stable 1,4-disubstituted 1,2,3-triazoles as amide bond bioisosteres proved a promising strategy for improving the tumor-targeting properties of a truncated analog of minigastrin. In this study, we applied the previously studied structural modifications to improve the pharmacokinetic and pharmacodynamic properties of PP-F11N, a minigastrin analog currently in clinical trials. Novel minigastrins (NMGs) as analogs of PP-F11N with one or two amide bonds substituted by 1,2,3-triazoles were synthesized, radiolabeled with 177Lu3+, and subjected to full evaluation in vitro (cell internalization, receptor affinity, stability in blood plasma) and in vivo (stability, biodistribution, SPECT/CT imaging). NMGs with triazoles inserted between the amino acids DGlu10-Ala11 and/or Tyr12-Gly13 showed a significantly increased cellular uptake and affinity toward the CCK2R in vitro. Resistance against the metabolic degradation of the NMGs was comparable to those of the clinical candidate PP-F11N. Imaging by SPECT/CT and biodistribution studies demonstrated a higher uptake in CCK2R-positive tumors but also in the CCK2R-positive stomach. The peptidomimetic compounds showed a slow tumor washout and high tumor-to-kidney ratios. The structural modifications led to the identification of analogs with promising properties for progression to clinical applications in the diagnosis and therapy of CCK2R-positive neoplasms.

In Search of a Role for Extracellular Purine Enzymes in Bone Function

Bone is one of the major tissues that undergoes continuous remodeling throughout life, thus ensuring both organic body growth during development and protection of internal organs as well as repair of trauma during adulthood. Many endogenous substances contribute to bone homeostasis, including purines. Their role has increasingly emerged in recent decades as compounds which, by interacting with specific receptors, can help determine adequate responses of bone cells to physiological or pathological stimuli. Equally, it is recognized that the activity of purines is closely dependent on their interconversion or metabolic degradation ensured by a series of enzymes present at extracellular level as predominantly bound to the cell membrane or, also, as soluble isoforms. While the effects of purines mediated by their receptor interactions have sufficiently, even though not entirely, been characterized in many tissues including bone, those promoted by the extracellular enzymes providing for purine metabolism have not been. In this review, we will try to circumstantiate the presence and the role of these enzymes in bone to define their close relationship with purine activities in maintaining bone homeostasis in normal or pathological conditions.

Fluoroalkylation of Dextromethorphan Improves CNS Exposure and Metabolic Stability

<p>Aryl-methyl ethers, while present in many bioactive compounds, are subject to rapid O-dealkylation that can generate bio-inactive or toxic metabolites. As an example, the cough suppressant dextromethorphan undergoes such a P450 mediated O-dealkylation to provide the psychoactive phenolic metabolite dextrorphan. This metabolite antagonizes the NMDA receptor causing hallucinations, which encourages recreational abuse. To circumvent this undesired metabolism, we have designed, synthesized, and evaluated <i>in vitro </i>and <i>in vivo</i> new fluoroalkyl analogs of dextromethorphan that display improved pharmacokinetic profiles relative to dextromethorphan and related analogs currently in clinical trials. Specifically, the fluorinated analogs minimized metabolic degradation and increased CNS exposure relative to DXM <i>in vivo</i>. Ultimately, these fluorinated motifs might be applicable to other aryl-methyl ether containing compounds as a strategy to improve pharmacokinetic profiles.<b></b></p>