Prodrugs of vitamin E. 1. Preparation and enzymatic hydrolysis of aminoalkanecarboxylic acid esters of d‐α‐tocopherol

Jiro Takata, Yoshiharu Karube, Yoshiko Itoh, Yoshikazu Matsushima

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Nine aminoalkanecarboxylic acid esters of d‐a‐tocopherol were synthesized and evaluated as potential water‐soluble prodrugs suitable for parenteral administration. The hydrochloric acid salts of the esters were soluble in water. The kinetics of hydrolysis of the esters was studied in isotonic phosphate buffer, rat plasma, human plasma, and rat liver homogenate at 37°C. The hydrolysis of the esters was proved to be catalyzed by liver esterases. The susceptibility of the esters to undergo liver esterase hydrolysis was affected by the structure of the amino functionality and size of the acyl moiety on the promoiety. The N‐methylaminoacetyl and N, N‐dimethylaminoacetyl esters of d‐α‐tocopherol were more rapidly hydrolyzed than d‐α‐tocopheryl acetate, a commercially available d‐α‐tocopheryl ester. These results suggested that the salts of the N, N‐dimethylaminoacetyl esters are promising prodrug candidates of d‐α‐tocopheryl for parenteral use.

Original languageEnglish
Pages (from-to)96-100
Number of pages5
JournalJournal of Pharmaceutical Sciences
Volume84
Issue number1
DOIs
Publication statusPublished - 1995

Fingerprint

Prodrugs
Vitamin E
Esters
Hydrolysis
Acids
Esterases
Liver
Salts
Hydrochloric Acid
Buffers
Acetates
Phosphates
Water

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Prodrugs of vitamin E. 1. Preparation and enzymatic hydrolysis of aminoalkanecarboxylic acid esters of d‐α‐tocopherol. / Takata, Jiro; Karube, Yoshiharu; Itoh, Yoshiko; Matsushima, Yoshikazu.

In: Journal of Pharmaceutical Sciences, Vol. 84, No. 1, 1995, p. 96-100.

Research output: Contribution to journalArticle

@article{1b52d1297b924c18856fbc1141a1e011,
title = "Prodrugs of vitamin E. 1. Preparation and enzymatic hydrolysis of aminoalkanecarboxylic acid esters of d‐α‐tocopherol",
abstract = "Nine aminoalkanecarboxylic acid esters of d‐a‐tocopherol were synthesized and evaluated as potential water‐soluble prodrugs suitable for parenteral administration. The hydrochloric acid salts of the esters were soluble in water. The kinetics of hydrolysis of the esters was studied in isotonic phosphate buffer, rat plasma, human plasma, and rat liver homogenate at 37°C. The hydrolysis of the esters was proved to be catalyzed by liver esterases. The susceptibility of the esters to undergo liver esterase hydrolysis was affected by the structure of the amino functionality and size of the acyl moiety on the promoiety. The N‐methylaminoacetyl and N, N‐dimethylaminoacetyl esters of d‐α‐tocopherol were more rapidly hydrolyzed than d‐α‐tocopheryl acetate, a commercially available d‐α‐tocopheryl ester. These results suggested that the salts of the N, N‐dimethylaminoacetyl esters are promising prodrug candidates of d‐α‐tocopheryl for parenteral use.",
author = "Jiro Takata and Yoshiharu Karube and Yoshiko Itoh and Yoshikazu Matsushima",
year = "1995",
doi = "10.1002/jps.2600840122",
language = "English",
volume = "84",
pages = "96--100",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Prodrugs of vitamin E. 1. Preparation and enzymatic hydrolysis of aminoalkanecarboxylic acid esters of d‐α‐tocopherol

AU - Takata, Jiro

AU - Karube, Yoshiharu

AU - Itoh, Yoshiko

AU - Matsushima, Yoshikazu

PY - 1995

Y1 - 1995

N2 - Nine aminoalkanecarboxylic acid esters of d‐a‐tocopherol were synthesized and evaluated as potential water‐soluble prodrugs suitable for parenteral administration. The hydrochloric acid salts of the esters were soluble in water. The kinetics of hydrolysis of the esters was studied in isotonic phosphate buffer, rat plasma, human plasma, and rat liver homogenate at 37°C. The hydrolysis of the esters was proved to be catalyzed by liver esterases. The susceptibility of the esters to undergo liver esterase hydrolysis was affected by the structure of the amino functionality and size of the acyl moiety on the promoiety. The N‐methylaminoacetyl and N, N‐dimethylaminoacetyl esters of d‐α‐tocopherol were more rapidly hydrolyzed than d‐α‐tocopheryl acetate, a commercially available d‐α‐tocopheryl ester. These results suggested that the salts of the N, N‐dimethylaminoacetyl esters are promising prodrug candidates of d‐α‐tocopheryl for parenteral use.

AB - Nine aminoalkanecarboxylic acid esters of d‐a‐tocopherol were synthesized and evaluated as potential water‐soluble prodrugs suitable for parenteral administration. The hydrochloric acid salts of the esters were soluble in water. The kinetics of hydrolysis of the esters was studied in isotonic phosphate buffer, rat plasma, human plasma, and rat liver homogenate at 37°C. The hydrolysis of the esters was proved to be catalyzed by liver esterases. The susceptibility of the esters to undergo liver esterase hydrolysis was affected by the structure of the amino functionality and size of the acyl moiety on the promoiety. The N‐methylaminoacetyl and N, N‐dimethylaminoacetyl esters of d‐α‐tocopherol were more rapidly hydrolyzed than d‐α‐tocopheryl acetate, a commercially available d‐α‐tocopheryl ester. These results suggested that the salts of the N, N‐dimethylaminoacetyl esters are promising prodrug candidates of d‐α‐tocopheryl for parenteral use.

UR - http://www.scopus.com/inward/record.url?scp=0029587362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029587362&partnerID=8YFLogxK

U2 - 10.1002/jps.2600840122

DO - 10.1002/jps.2600840122

M3 - Article

VL - 84

SP - 96

EP - 100

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 1

ER -