Oxidation of carbidopa by tyrosinase and its effect on murine melanoma

Gąsowska-Bajger, Beata; Frąckowiak-Wojtasek, Bożena; Koj, Sabina; Cichoń, Tomasz; Smolarczyk, Ryszard; Szala, Stanisław; Wojtasek, Hubert

doi:10.1016/j.bmcl.2009.05.002

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…Given that both LD and CD are known to be susceptible to oxidative or decarboxylative degradation, 15,16 the longterm stability of solutions of foslevodopa and foscarbidopa was assessed. In oxygen-protected conditions, foslevodopa and foscarbidopa were observed to be stable (<2% change in foslevodopa and foscarbidopa assay values) for >1 year in solution at high concentrations (eg, 240/12 and 360/18mg/ml) across a wide pH range (6.5-9.2) including the physiological pH of 7.4.…”

Section: Chemical Stabilitymentioning

confidence: 99%

Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease

Rosebraugh

Voight

Moussa

et al. 2021

Annals of Neurology

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The aim was to demonstrate that continuous s.c. infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via a minimally invasive and convenient mode and has the potential to treat Parkinson's disease (PD) patients who are not well controlled on oral medication. Methods: Foslevodopa and foscarbidopa were prepared and the equilibrium solubility and chemical stability examined in aqueous media with different values of pH. Solutions of foslevodopa/foscarbidopa (ratios ranging from 4:1 to 20:1) were prepared by dissolving pH-adjusted lyophilized materials in water and infused s.c. in healthy volunteers for ≤72 hours. Frequent blood samples were collected to measure LD and CD exposure, and safety was monitored throughout the study. Results: Foslevodopa/foscarbidopa (ABBV-951) demonstrates high water solubility and excellent chemical stability near physiological pH, enabling continuous s.c. infusion therapy. After s.c. infusion, a stable LD pharmacokinetic (PK) profile was maintained for ≤72 hours, and the infusion was well tolerated. Interpretation: Preparation of foslevodopa and foscarbidopa enables preclinical and clinical PK, safety, and tolerability studies in support of their advancement for the treatment of PD. In phase 1 clinical trials, foslevodopa/foscarbidopa demonstrates consistent and stable LD plasma exposure, supporting further studies of this treatment as a potentially transformational option for those suffering from PD.

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Section: Chemical Stabilitymentioning

confidence: 99%

Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease

Rosebraugh

Voight

Moussa

et al. 2021

Annals of Neurology

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“…Similarly, the lone pair donation from the nitrogen atom to the pyrrole ring of indole-3-carbaldehyde (I3A) delocalizes the formyl charge by resonance (Figure 4c). Together with the azine, a molecule of 3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid should be formed, likely through a carbocation intermediate that should lead to the loss of chirality, previously identified as a metabolite of carbidopa [27,30].…”

Section: Proposed Mechanism Of Reaction Of Selected Aldehydes and Car...mentioning

confidence: 99%

Quantitative Colorimetric Sensing of Carbidopa in Anti-Parkinson Drugs Based on Selective Reaction with Indole-3-Carbaldehyde

Palladino,

Rainetti,

Lettieri

et al. 2023

Sensors

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The quality of life of patients affected by Parkinson’s disease is improved by medications containing levodopa and carbidopa, restoring the dopamine concentration in the brain. Accordingly, the affordable quality control of such pharmaceuticals is very important. Here is reported the simple and inexpensive colorimetric quantification of carbidopa in anti-Parkinson drugs by the selective condensation reaction between the hydrazine group from carbidopa and the formyl functional group of selected aldehydes in acidified hydroalcoholic solution. An optical assay was developed by using indole-3-carbaldehyde (I3A) giving a yellow aldazine in EtOH:H2O 1:1 (λmax~415 nm) at 70 °C for 4 h, as confirmed by LC-MS analysis. A filter-based plate reader was used for colorimetric data acquisition, providing superior results in terms of analytical performances for I3A, with a sensitivity ~50 L g−1 and LOD ~0.1 mg L−1 in comparison to a previous study based on vanillin, giving, for the same figures of merit values, about 13 L g−1 and 0.2–0.3 mg L−1, respectively. The calibration curves for the standard solution and drugs were almost superimposable, therefore excluding interference from the excipients and additives, with very good reproducibility (avRSD% 2–4%) within the linear dynamic range (10 mg L−1–50 mg L−1).

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“…hydroxytyrosol) (Botta et al 2015), production of prodrugs (e.g. L-DOPA) (Kampmann et al 2016) or compounds suppressing melanoma (Gąsowska-Bajger et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Effectivity of tyrosinase purification by membrane techniques versus fractionation by salting out

et al. 2020

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The main goal of this study was to select micro-and ultrafiltration membranes that can be used for the purification of mushroom tyrosinase, replacing salting-out dual-step processes followed by centrifugations. In experiments, a raw extract from white mushrooms was used with high level of ballast proteins and brownish impurities. Four microfiltration membranes for the removal of undesired high molecular weight compounds were screened and that made of nitrocellulose was selected due to high recovery of enzymatic activity. Then diafiltration and concentration on the membrane made of polyethersulphone (300 kDa) was selected to recover 8% of proteins and 58% of tyrosinase activity with five-to seven purification fold, 10% of proteases, and 8% of brown impurities. It was shown that tyrosinase can be pre-purified by selected membranes yielding the enzyme quality at least comparable to that after double salting-out method but in one device. In both cases, subsequent purification by ion-exchange chromatography slightly increased purification degree of the enzyme and brown impurity removal. The surplus of membrane pre-purification is substantially higher thermal stability of the enzyme, enlarged after the chromatographic step, due to very low content of proteolytic enzymes.

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Oxidation of carbidopa by tyrosinase and its effect on murine melanoma

Cited by 5 publications

References 16 publications

Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease

Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease

Quantitative Colorimetric Sensing of Carbidopa in Anti-Parkinson Drugs Based on Selective Reaction with Indole-3-Carbaldehyde

Effectivity of tyrosinase purification by membrane techniques versus fractionation by salting out

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