Design, synthesis and biological evaluation of water-soluble phenytoin prodrugs considering the substrate recognition ability of human carboxylesterase 1

Takahashi, Masato; Lee, Yeon Joo; Kanayama, Teruhiko; Kondo, Yûsuke; Nishio, Kazuto; Mukai, Kota; Haba, Masami; Hosokawa, Masakiyo

doi:10.1016/j.ejps.2020.105455

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…Among the prodrugs of Haloperidol, the branched-chain and small chain exhibit sustained release behavior. The alcohol ester prodrugs showed a similar activation rate both in Human Liver Microsome solution and human carboxylesterase solution, whereas pentanoate and hexanoate prodrug of Haloperidol show high rates of metabolic activation (42).…”

Section: Developments In Prodrug Designingmentioning

confidence: 89%

Current Drifts in Design and Development of Prodrugs

Krishna

Shah

2022

ECS Trans.

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The design and development of prodrug is based on the objectivity to improve the pharmacokinetic and pharmacodynamic profiles including toxicity of the potent chemical entity. Currently, the prodrug approach is extended with conjugating the parent drug with a self immolating molecule or linker which itself assembles into nanoparticles and prolonged the blood circulation and having passive targeting ability. It also includes delivery of the drug at target site having specific pH condition, delivery of drug to brain by endogenous carrier molecule, NQO1 activable prodrug, prodrug with sustained release behavior, receptor targeted, dual action prodrug, activation via specific enzyme like human carboxylesterase, and phospholipase A2. Some other approaches to prodrug development are that the conversion of active pharmaceutical ingredient (API) into ionic liquids (ILs). In this the biocompatible ionic liquids include choline and amino acid esters are used. One of the anticancer drug methotrexate is formulated into ionic liquid form and used as potential anticancer prodrug. In addition to improvement in combination chemotherapy, there is photoresponsive hybrid prodrug that consists of a photoremovable protecting group. The release of doxorubicin and combrestatin A4 is mainly triggered by 405 nm light and 365 nm light respectively and displayed a quasi-sequential release behavior.

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Section: Developments In Prodrug Designingmentioning

confidence: 89%

Current Drifts in Design and Development of Prodrugs

Krishna

Shah

2022

ECS Trans.

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“…mCes2c is mainly expressed in the colon but is also present in the duodenum, the ileum, the jejunum, and the liver. Thus, mCes2c partially shows an expression pattern similar to that of hCES2, which is expressed in the small intestine, kidney and liver, whereas hCES1 expression occurs mainly in the liver and lung [ 6 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

The Crystal Structure of Mouse Ces2c, a Potential Ortholog of Human CES2, Shows Structural Similarities in Substrate Regulation and Product Release to Human CES1

Eisner

Riegler-Berket

Gamez

et al. 2022

IJMS

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Members of the carboxylesterase 2 (Ces2/CES2) family have been studied intensively with respect to their hydrolytic function on (pro)drugs, whereas their physiological role in lipid and energy metabolism has been realized only within the last few years. Humans have one CES2 gene which is highly expressed in liver, intestine, and kidney. Interestingly, eight homologous Ces2 (Ces2a to Ces2h) genes exist in mice and the individual roles of the corresponding proteins are incompletely understood. Mouse Ces2c (mCes2c) is suggested as potential ortholog of human CES2. Therefore, we aimed at its structural and biophysical characterization. Here, we present the first crystal structure of mCes2c to 2.12 Å resolution. The overall structure of mCes2c resembles that of the human CES1 (hCES1). The core domain adopts an α/β hydrolase-fold with S230, E347, and H459 forming a catalytic triad. Access to the active site is restricted by the cap, the flexible lid, and the regulatory domain. The conserved gate (M417) and switch (F418) residues might have a function in product release similar as suggested for hCES1. Biophysical characterization confirms that mCes2c is a monomer in solution. Thus, this study broadens our understanding of the mammalian carboxylesterase family and assists in delineating the similarities and differences of the different family members.

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“…Most of the MP and its derivatives for MPHS and 17-MPHS conducted an HPLC analysis method using a high percentage of the organic modifiers from methanol, acetonitrile, special reagents such as chloroform, tetrahydrofuran, butyl chloride, tetrabutylammonium hydroxide, adjusted pH buffer solutions, gradient program 7 , 8 , 14 – 17 , special type of separation HPLC column 6 , using guard column cartridge 14 . Additionally, the separation process is a time consumed.…”

Section: Introductıonmentioning

confidence: 99%

A new validated facile HPLC analysis method to determine methylprednisolone including its derivatives and practical application

Al-Hakkani

2023

Sci Rep

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Methylprednisolone sodium succinate (MPSS) is a parenteral water-soluble corticosteroid ester. It gives three peaks methylprednisolone (MP), 17-methylprednisolone hemisuccinate (17-MPHS), and methylprednisolone hemisuccinate (MPHS) that share in the assay determination as total MP. It is used on a wide scale in prescribed anti-inflammatory drugs as a common use. The current study aimed to find a rapid RP-HPLC method of MP and its derivatives analysis with high linearity, repeatability, sensitivity, selectivity, and inexpensive to use without the need for any special chemical reagents. The use of the current method achieved a satisfactory result to detect, determine and separate the MP, 17-MPHS, and MPHS in a short time. The chromatographic system consists of RP-HPLC using the BDS column (250 mm × 4.6 mm × 5 μm). The mobile phase was prepared by mixing the WFI: glacial acetic acid: acetonitrile in a volume ratio (63:2:35) at a flow rate of 2.0 mL/min with detection wavelength at 254 nm at room temperature and injection volume 20 μL. The method manifested a satisfied linearity regression R2 (0.9998–0.99999) with LOD 143.97 ng/mL and 4.49 µg/mL; and LOQ 436.27 ng/mL and 13.61 µg/mL for MP and MPHS respectively. The method proved its efficiency via system suitability achievement in the robustness and ruggedness conduction according to the validation guidelines. High sensitivity according to its LOD and LOQ. So, the current method could be considered in the pharmaceutical industry. The suggested method has been successfully implemented in the Egyptian local market for the quantitative assessment of the assay of the finished product.

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Design, synthesis and biological evaluation of water-soluble phenytoin prodrugs considering the substrate recognition ability of human carboxylesterase 1

Cited by 7 publications

References 35 publications

Current Drifts in Design and Development of Prodrugs

Current Drifts in Design and Development of Prodrugs

The Crystal Structure of Mouse Ces2c, a Potential Ortholog of Human CES2, Shows Structural Similarities in Substrate Regulation and Product Release to Human CES1

A new validated facile HPLC analysis method to determine methylprednisolone including its derivatives and practical application

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