An Improved Synthesis of 4'-Hydroxydiclofenac

Kim, Sang Hyun; Kwon, Jung Hwan; Yoon, Sung Hwa

doi:10.5012/bkcs.2010.31.10.3007

Cited by 8 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the percentage accuracy of the three concentration levels of 4′-hydroxydiclofenac met the ICH guidelines (80–120%). Thus, our finding demonstrated that the 4′-hydroxydiclofenac solution was relatively stable for three consecutive days in the rat liver microsomes at room temperature, which is in agreement with the literature [ 21 ].…”

Section: Resultssupporting

confidence: 92%

Development and Validation of an HPLC-UV Method for the Quantification of 4′-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug–Drug Interaction in Rat Liver Microsomes

Salhab

Barker

2022

Molecules

View full text Add to dashboard Cite

Salicylic acid is a key compound in nonsteroidal anti-inflammatory drugs that has been recently used for preventing the risk of hospitalization and death among COVID-19 patients and in preventing colorectal cancer (CRC) by suppressing two key proteins. Understanding drug–drug interaction pathways prevent the occurrence of adverse drug reactions in clinical trials. Drug–drug interactions can result in the variation of the pharmacodynamics and pharmacokinetic of the drug. Inhibition of the Cytochrome P450 enzyme activity leads to the withdrawal of the drug from the market. The aim of this paper was to develop and validate an HPLC-UV method for the quantification of 4′-hydroxydiclofenac as a CYP2C9 metabolite using salicylic acid as an inhibitor in rat liver microsomes. A CYP2C9 assay was developed and validated on the reversed phase C18 column (SUPELCO 25 cm × 4.6 mm × 5 µm) using a low-pressure gradient elution programming at T = 30 °C, a wavelength of 282 nm, and a flow rate of 1 mL/min. 4′-hydroxydiclofenac demonstrated a good linearity (R2 > 0.99), good reproducibility, low detection, and quantitation limit, and the inter and intra-day precision met the ICH guidelines (<15%). 4′-hydroxydiclofenac was stable for three days and showed an acceptable accuracy and recovery (80–120%) within the ICH guidelines in a rat liver microsome sample. This method will be beneficial for future applications of the in vitro inhibitory effect of salicylic acid on the CYP2C9 enzyme activity in rat microsomes and the in vivo administration of salicylic acid in clinical trials.

show abstract

Section: Resultssupporting

confidence: 92%

Development and Validation of an HPLC-UV Method for the Quantification of 4′-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug–Drug Interaction in Rat Liver Microsomes

Salhab

Barker

2022

Molecules

View full text Add to dashboard Cite

show abstract

“…The product was identified as 4`hydroxydiclofenac by matching its NMR data to that reported in the literature (Scheme 3). 46,47 Scheme 3 The product formed from the CYP101B1 turnover with diclofenac. The numbering system used for diclofenac is the same as that from Marco-Urrea et al 46 As a control we tested diphenylmethane with the CYP101B1 enzyme.…”

Section: Please Do Not Adjust Marginsmentioning

confidence: 99%

The selective oxidation of substituted aromatic hydrocarbons and the observation of uncoupling via redox cycling during naphthalene oxidation by the CYP101B1 system

Hall

Sarkar

Bell

2017

Catal. Sci. Technol.

View full text Add to dashboard Cite

show abstract

“…; Kim et al. ). Synthesis of drug metabolites involves time‐consuming, high‐cost and challenging production processes, resulting in expensive compounds, when available.…”

Section: Introductionmentioning

confidence: 98%

Oxyfunctionalization of nonsteroidal anti‐inflammatory drugs by filamentous‐fungi

et al. 2019

View full text Add to dashboard Cite

Aims:We aimed to expand the microbial biocatalyst platform to generate essential oxyfunctionalized standards for pharmaceutical, toxicological and environmental research. In particular, we examined the production of oxyfunctionalized nonsteroidal anti-inflammatory drugs (NSAIDs) by filamentous-fungi. Methods and Results: Four NSAIDs; diclofenac, ibuprofen, naproxen and mefenamic acid were used as substrates for oxyfunctionalization in a biocatalytic process involving three filamentous-fungi strains; Beauveria bassiana, Clitocybe nebularis and Mucor hiemalis. Oxyfunctionalized metabolites that are major degradation intermediates formed by Cytochrome P450 monooxygenases in human metabolism were produced in isolated yields of up to 99% using 1 g l À1 of substrate. In addition, a novel compound, 3 0 ,4 0dihydroxydiclofenac, was produced by B. bassiana. Proteomic analysis identified CYP548A5 that might be responsible for diclofenac oxyfunctionalization in B. bassiana. Conclusions: Efficient fungi catalysed oxyfunctionalization was achieved when using NSAIDs as substrates. High purities and isolated yields of the produced metabolites were achieved. Significance and Impact of the Study: The lack of current efficient synthetic strategies for oxyfunctionalization of NSAIDs is a bottleneck to perform pharmacokinetic, pharmacodynamic and toxicological analysis for the pharmaceutical industry. Additionally, oxyfunctionalized derivatives are needed for tracking the fate and impact of such metabolites in the environment. Herein, we described a fungi catalysed process that surpasses previously reported strategies in terms of efficiency, to synthesize oxyfunctionalized NSAIDs.

show abstract

An Improved Synthesis of 4'-Hydroxydiclofenac

Cited by 8 publications

References 14 publications

Development and Validation of an HPLC-UV Method for the Quantification of 4′-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug–Drug Interaction in Rat Liver Microsomes

Development and Validation of an HPLC-UV Method for the Quantification of 4′-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug–Drug Interaction in Rat Liver Microsomes

The selective oxidation of substituted aromatic hydrocarbons and the observation of uncoupling via redox cycling during naphthalene oxidation by the CYP101B1 system

Oxyfunctionalization of nonsteroidal anti‐inflammatory drugs by filamentous‐fungi

Contact Info

Product

Resources

About