Biomodification of acenocoumarol by bifidobacteria

2021 ◽  
Vol 368 (18) ◽  
Author(s):  
Melisa Fragomeno ◽  
Sabrina Assad ◽  
Pablo Mobili ◽  
Pablo J Peruzzo ◽  
Jessica Minnaard ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Bifidobacterium Bifidum ◽  
Pharmacological Properties ◽  
Anaerobic Conditions ◽  
Bifidobacterium Adolescentis ◽  
Rp Hplc ◽  
Narrow Therapeutic Range ◽  
Culture Supernatants ◽  
Mrs Broth

ABSTRACT The increased interest of consumers in probiotic foods requires a deeper knowledge on the possible interactions with drugs, because their pharmacological properties could be modified. In this context, these studies are relevant for drugs such as acenocoumarol, whose dosage must be controlled due to, among other factors, food-drug interactions. Acenocoumarol is an oral anticoagulant with a narrow therapeutic range. The aim of the present research is to evaluate, in vitro, the effect of bifidobacteria on acenocoumarol. The drug was incubated with Bifidobacterium bifidum CIDCA 5310 or Bifidobacterium adolescentis CIDCA 5317 in MRS broth at 37°C for 24 h in anaerobic conditions. The effect of incubation with sterilized spent culture supernatants (SSCS) was also evaluated. Analysis by RP-HPLC showed that both bifidobacterial strains reduced the area of the acenocoumarol peak and two new peaks were evidenced. In addition, a decrease in the intensity of the bands at 1650, 1390 and 1110/cm was observed in the FTIR spectroscopic determinations. Moreover, a new band appeared at 1720/cm. No effect on the drug was observed when incubation was performed with SSCS. The present study showed a significant change in the concentration of the anticoagulant after incubation with bifidobacteria and results are compatible with biomodification of the drug due to enzymatic activity of bifidobacteria.

scholarly journals Stability of Alteplase for Catheter-Directed, Ultrasound-Facilitated Thrombolysis

2021 ◽  
Author(s):  
John Fanikos ◽  
Kathleen Marquis ◽  
Leo Francis Buckley ◽  
Lena Kim Tran ◽  
Kevin C McLaughlin ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
High Performance ◽  
In Vitro Study ◽  
Bleeding Risk ◽  
Reversed Phase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rp Hplc ◽  
Catheter Directed Thrombolysis ◽  
Over Time

Introduction Ultrasound-facilitated catheter-directed thrombolysis is used with low-dose alteplase to treat pulmonary embolism. This reduces the bleeding risk that accompanies systemic administration of higher alteplase doses. While studies suggest that alteplase given over 2 to 6 hours is safe and effective, few data exist to support alteplase stability under these conditions. Therefore, we undertook this in vitro study to determine the duration of alteplase stability. Methods Alteplase was prepared in solutions of 8 mg in 100 mL, 6 mg in 150 mL, and 8 mg in 200 mL. Solutions were administered through the EkoSonicTM Endovascular System with and without ultrasound, to simulate administration over 2, 4, and 6 hours. Alteplase was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). Assays were performed at time 0 and at 30-minute intervals during simulated infusion. An enzyme-linked immunosorbent assay (ELISA) assay was used to measure alteplase concentrations that were at time 0 and at 15-minute intervals during simulated infusion. Results Using RP-HPLC, in the absence of ultrasound, the alteplase concentration remained within 1% of the original concentration through 120, 240, and 360 minutes of infusion. Using RP-HPLC for measurement, alteplase, in the presence of ultrasound, degraded steadily over time to approximately 90%, 80%, and 70% of its original amounts in 120, 240, and 360 minutes, respectively. Alteplase that remained was available for enzymatic activity. Conclusions Alteplase solutions of 0.04 and 0.08 mg/mL degraded steadily over time during simulated ultrasound-facilitated catheter-directed administration. Alteplase that did not degrade remained available for enzymatic activity.

Investigating bifidobacteria and human milk oligosaccharide composition of lactating mothers

2020 ◽  
Vol 96 (5) ◽  
Author(s):  
Gabriele Andrea Lugli ◽  
Sabrina Duranti ◽  
Christian Milani ◽  
Leonardo Mancabelli ◽  
Francesca Turroni ◽  
...  
Keyword(s):  
Human Milk ◽  
Intestinal Tract ◽  
Bifidobacterium Longum ◽  
Bifidobacterium Bifidum ◽  
Metagenomic Data ◽  
Bifidobacterium Adolescentis ◽  
Milk Samples ◽  
Flow Cytometric ◽  
Lactating Mothers

ABSTRACT Human milk is known to carry its own microbiota, of which the precise origin remains obscure. Breastfeeding allows mother-to-baby transmission of microorganisms as well as the transfer of many other milk components, such as human milk oligosaccharides (HMOs), which act as metabolizable substrates for particular bacteria, such as bifidobacteria, residing in infant intestinal tract. In the current study, we report the HMO composition of 249 human milk samples, in 163 of which we quantified the abundance of members of the Bifidobacterium genus using a combination of metagenomic and flow cytometric approaches. Metagenomic data allowed us to identify four clusters dominated by Bifidobacterium adolescentis and Bifidobacterium pseudolongum, Bifidobacterium crudilactis or Bifidobacterium dentium, as well as a cluster represented by a heterogeneous mix of bifidobacterial species such as Bifidobacterium breve and Bifidobacterium longum. Furthermore, in vitro growth assays on HMOs coupled with in silico glycobiome analyses allowed us to elucidate that members of the Bifidobacterium bifidum and B. breve species exhibit the greatest ability to degrade and grow on HMOs. Altogether, these findings indicate that the bifidobacterial component of the human milk microbiota is not strictly correlated with their ability to metabolize HMOs.

scholarly journals THE EFFECT OF Agrobacterium tumefaciens STRAINS ON CALLUS INDUCED FROM THE SHOOT TIPS OF GINGER (Zingiber Officinale var. Roscoe) IN THE PRODUCTION OF SOME MEDICINAL ACTIVE COMPOUNDS ESTIMATED BY RP-HPLC

2020 ◽  
Vol 17 (36) ◽  
pp. 706-719
Author(s):  
Abdulelah Abdulhussain AL-MAYAH ◽  
Huda Abdulkreem AL-TAHA ◽  
Widad Ali Abd AL-BEHADILI
Keyword(s):  
Agrobacterium Tumefaciens ◽  
Medicinal Plant ◽  
Callus Tissue ◽  
Zingiber Officinale ◽  
Shoot Tips ◽  
Drug Preparation ◽  
Pharmacological Properties ◽  
Active Compounds ◽  
Rp Hplc

Ginger (Zingiber officinale var. Roscoe) is a medicinal plant well known for its pharmacological properties. This research aimed to study the effect of different concentrations of Agrobacterium tumefaciens bacteria on callus induced from the shoot tips of ginger in the production of some active medicinal compounds. Callus was induced from the cultivation of half-buds in MS with 2,4-D at a concentration of 1 mg/L with BA at a concentration of 0.5 mg/L + 500 mg/L PVP. It was the best medium for induced callus. A total of 100 mg of developing callus was taken, and, after cultivation on the same medium, at two weeks of age, the callus was treated with two strains of Agrobacterium LBA4404 and C58 and three concentrations of 101, 103, and 105 bacteria/mL each trial. The analysis of RP-HPLC showed that when treated with LBA4404 strain, which was at the concentration of 105 bacteria/mL, the highest increase in the amount of Zingerone reached 0.278 mg/g, followed by a concentration of 101 bacteria/mL and which gave the highest concentration of Zingerone, 6-gingerol, and 6-Shogaol which were 0.199, 0.099 and 0.069 mg/g respectively. As for the C58 strain, the treatment recorded 101 bacteria /mL, the highest concentration of Zingerone 0.240 mg/g, followed by a concentration of 103 bacteria /mL, which was significantly superior in giving the highest concentration of 6-gingerol and 6-Shogaol, which reached 0.053 and 0.027 mg/g respectively. From the results of the experiment, it can be considered that the active medical compounds produced by the induced callus tissue in vitro can increase when exposed to biological stimuli, as the medicinally active compounds can be separated, purified and used in a pure form as they are a natural source for drug preparation.

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

2019 ◽  
Vol 20 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Abdullah M. Alnuqaydan ◽  
Bilal Rah
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
In Vivo Model ◽  
Drug Candidate ◽  
Phytochemical Analysis ◽  
Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

Traceable Peptidic Ligands that Target Ghrelin Receptors

2020 ◽  
Vol 21 (10) ◽  
pp. 955-964 ◽  
Author(s):  
Mengjie Liu ◽  
John Wade ◽  
Mohammed Akhter Hossain
Keyword(s):  
In Vivo Imaging ◽  
Peptide Hormone ◽  
Structural Features ◽  
Pharmacological Properties ◽  
Imaging Studies ◽  
Cognate Receptor ◽  
Ghrelin Receptors ◽  
Biochemical Research

: Ghrelin is a 28-amino acid octanoylated peptide hormone that is implicated in many physiological and pathophysiological processes. Specific visualization of ghrelin and its cognate receptor using traceable ligands is crucial in elucidating the localization, functions, and expression pattern of the peptide’s signaling pathway. Here 12 representative radio- and fluorescently-labeled peptide-based ligands are reviewed for in vitro and in vivo imaging studies. In particular, the focus is on their structural features, pharmacological properties, and applications in further biochemical research.

In-vitro Kinetic Hydrolysis Study of Metronidazole Derivatives with Carvacrol and Eugenol Using Validated RP-HPLC Method

2020 ◽  
Vol 16 ◽  
Author(s):  
M. Alarjah
Keyword(s):  
Half Life ◽  
Hplc Method ◽  
Hydrolysis Rate ◽  
First Order ◽  
First Order Kinetics ◽  
Rp Hplc ◽  
Pharmacokinetic Properties ◽  
Pseudo First Order ◽  
Kinetic Hydrolysis

Background: Prodrugs principle is widely used to improve the pharmacological and pharmacokinetic properties of some active drugs. Much effort was made to develop metronidazole prodrugs to enhance antibacterial activity and or to improve pharmacokinetic properties of the molecule or to lower the adverse effects of metronidazole. Objective: In this work, the pharmacokinetic properties of some of monoterpenes and eugenol pro metronidazole molecules that were developed earlier were evaluated in-vitro. The kinetic hydrolysis rate constants and half-life time estimation of the new metronidazole derivatives were calculated using the validated RP-HPLC method. Method: Chromatographic analysis was done using Zorbbax Eclipse eXtra Dense Bonding (XDB)-C18 column of dimensions (250 mm, 4.6 mm, 5 μm), at ambient column temperature. The mobile phase was a mixture of sodium dihydrogen phosphate buffer of pH 4.5 and methanol in gradient elution, at 1ml/min flow rate. The method was fully validated according to the International Council for Harmonization (ICH) guidelines. The hydrolysis process carried out in an acidic buffer pH 1.2 and in an alkaline buffer pH 7.4 in a thermostatic bath at 37ºC. Results: The results followed pseudo-first-order kinetics. All metronidazole prodrugs were stable in the acidic pH, while they were hydrolysed in the alkaline buffer within a few hours (6-8 hr). The rate constant and half-life values were calculated, and their values were found to be 0.082- 0.117 hr-1 and 5.9- 8.5 hr., respectively. Conclusion: The developed method was accurate, sensitive, and selective for the prodrugs. For most of the prodrugs, the hydrolysis followed pseudo-first-order kinetics; the method might be utilised to conduct an in-vivo study for the metronidazole derivatives with monoterpenes and eugenol.

Kinase Targets for Mycolic Acid Biosynthesis in Mycobacterium tuberculosis

2019 ◽  
Vol 12 (1) ◽  
pp. 27-49 ◽  
Author(s):  
Shahinda S.R. Alsayed ◽  
Chau C. Beh ◽  
Neil R. Foster ◽  
Alan D. Payne ◽  
Yu Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Enzymatic Activity ◽  
Bacterial Pathogen ◽  
Building Blocks ◽  
Mycolic Acid ◽  
Adaptive Responses ◽  
Mycolic Acids ◽  
Hydroxylated Fatty Acids

Background:Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercle bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic machineries involved in the biosynthesis of MAs in M.tb. However, gaps still remain in the exact role of the phosphorylation and dephosphorylation of regulatory mechanisms within these systems. To date, a total of 11 serine-threonine protein kinases (STPKs) are found in M.tb. Most enzymes implicated in the MAs synthesis were found to be phosphorylated in vitro and/or in vivo. For instance, phosphorylation of KasA, KasB, mtFabH, InhA, MabA, and FadD32 downregulated their enzymatic activity, while phosphorylation of VirS increased its enzymatic activity. These observations suggest that the kinases and phosphatases system could play a role in M.tb adaptive responses and survival mechanisms in the human host. As the mycobacterial STPKs do not share a high sequence homology to the human’s, there have been some early drug discovery efforts towards developing potent and selective inhibitors.Objective:Recent updates to the kinases and phosphatases involved in the regulation of MAs biosynthesis will be presented in this mini-review, including their known small molecule inhibitors.Conclusion:Mycobacterial kinases and phosphatases involved in the MAs regulation may serve as a useful avenue for antitubercular therapy.

scholarly journals PenA, a penicillin-binding protein-type thioesterase specialized for small peptide cyclization

2021 ◽  
Author(s):  
Kenichi Matsuda ◽  
Kei Fujita ◽  
Toshiyuki Wakimoto
Keyword(s):  
Enzymatic Activity ◽  
Computational Model ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Small Peptide ◽  
Peptide Cyclization ◽  
Chain Lengths ◽  
Non Ribosomal Peptides

Abstract Penicillin binding protein-type thioesterases (PBP-type TEs) are a recently identified group of peptide cyclases that catalyze head-to-tail macrolactamization of non-ribosomal peptides. PenA, a new member of this group, is involved in the biosyntheses of cyclic pentapeptides. In this study, we demonstrated the enzymatic activity of PenA in vitro, and analyzed its substrate scope with a series of synthetic substrates. A comparison of the reaction profiles between PenA and SurE, a representative PBP-type TE, showed that PenA is more specialized for small peptide cyclization. A computational model provided a possible structural rationale for the altered specificity for substrate chain lengths.

scholarly journals Hemisynthesis and Biological Evaluation of Cinnamylated, Benzylated, and Prenylated Dihydrochalcones from a Common Bio-Sourced Precursor

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 620
Author(s):  
Anne Ardaillou ◽  
Jérôme Alsarraf ◽  
Jean Legault ◽  
François Simard ◽  
André Pichette
Keyword(s):  
Biological Activities ◽  
Biological Evaluation ◽  
Pharmacological Properties ◽  
Cytotoxic Potential ◽  
Naturally Occurring

Several families of naturally occurring C-alkylated dihydrochalcones display a broad range of biological activities, including antimicrobial and cytotoxic properties, depending on their alkylation sidechain. The catalytic Friedel–Crafts alkylation of the readily available aglycon moiety of neohesperidin dihydrochalcone was performed using cinnamyl, benzyl, and isoprenyl alcohols. This procedure provided a straightforward access to a series of derivatives that were structurally related to natural balsacones, uvaretin, and erioschalcones, respectively. The antibacterial and cytotoxic potential of these novel analogs was evaluated in vitro and highlighted some relations between the structure and the pharmacological properties of alkylated dihydrochalcones.

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