Effects of 1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin on human aldose reductase examined by a new application of HPLC system for measuring tissue polyol.
M16209 (1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin, CAS 128851-36-5) displayed potent inhibitory effects upon recombinant human aldose reductase (rhAR, IC50 = 0.051 mumol/l). The inhibition of rhAR by M16209 was uncompetitive with respect to both glyceraldehyde and NADPH. The effects of M16209 on human AR were investigated using a new application of HPLC system developed for analysis of tissue polyol. M16209 and epalrestat suppressed galactitol accumulation in human erythrocytes cultured in 25 mmol/l galactose with IC50 values of 1.2 and 2.6 mumol/l, respectively. The new application of HPLC system equipped with an electrochemical detector did not require any derivatization procedure for polyols and enabled simultaneous determination of glucose, galactose, fructose, myo-inositol, galactitol and sorbitol.
Murakami
N
N
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan.
Ohta
M
M
Kato
K
K
Nakayama
K
K
Mizota
M
M
Miwa
I
I
Okuda
J
J
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004376:Galactitol / Q000097:blood; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011108:Polymers / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism
D001572:Benzofurans; D004791:Enzyme Inhibitors; D006827:Hydantoins; D011108:Polymers; D011994:Recombinant Proteins; C024617:polyol; D004376:Galactitol; C068409:M 16209; D000449:Aldehyde Reductase