Synthesis and evaluation of hydrogen peroxide sensitive tofacitinib prodrugs

Previtali, Viola; Keiding, Ulrik Bering; Olsen, Asger Hegelund; Cadahía, Jorge Peiró; Clausen, Anne Skovsbo; Kjær, Andreas; Andresen, Thomas Lars; Hansen, Anders Elias; Clausen, Mads H.

doi:10.1016/j.ejmcr.2021.100019

Cited by 1 publication

(2 citation statements)

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“…[ 32 ] It is known that the prodrugs containing a carbamate or carbon–nitrogen linker have a slower drug release rate due to the stable intermediate phenol conjugate. [ 47,48 ] Hence, to study the further degradation of prodrug (and consequently the 5‐FC release) under plasma‐induced reactive species, treated samples were incubated for 3 days and analyzed by UHPLC‐MS/MS using the same MRM mode. As shown in Figure 1, a longer incubation time partially impacted the liberation of the 5‐FC.…”

Section: Resultsmentioning

confidence: 99%

“…[32] It is known that the prodrugs containing a carbamate or carbon-nitrogen linker have a slower drug release rate due to the stable intermediate phenol conjugate. [47,48] Hence, to study the further degradation of prodrug (and consequently the 5-FC release) under plasma-induced S C H E M E 4 Proposed mechanism of 5-fluorocytosine (5-FC) release upon plasma treatment. The initial arylboronate ester 1 is first hydrolyzed accompanied by the release of pinacol and formation of bis-arylboronic acids (a).…”

Section: Prodrug Transformationsmentioning

confidence: 99%

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Flucytosine‐based prodrug activation by cold physical plasma

Ahmadi

Potlitz

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et al. 2022

Archiv der Pharmazie

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Reactive oxygen species (ROS) are known to trigger drug release from arylboronate‐containing ROS‐responsive prodrugs. In cancer cells, elevated levels of ROS can be exploited for the selective activation of prodrugs via Baeyer–Villiger type oxidation rearrangement sequences. Here, we report a proof of concept to demonstrate that these cascades can as well be initiated by cold physical plasma (CPP). An analog of a recently reported fluorouracil prodrug based on the less toxic drug 5‐fluorocytosine (5‐FC) was synthesized with a view to laboratory safety reasons and used as a model compound to prove our hypothesis that CPP is suitable as a trigger for the prodrug activation. Although the envisioned oxidation and rearrangement with successive loss of boronic acid species could be achieved by plasma treatment, the anticipated spontaneous liberation of 5‐FC was inefficient in the model case. However, the obtained results suggest that custom‐tailored CPP‐responsive prodrugs might become an evolving research field.

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Section: Resultsmentioning

confidence: 99%