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Biotransformation of flobufen enantiomers in ruminant hepatocytes and subcellular fractions
Author(s) -
Skálová Lenka,
Szotáková Barbora,
Lamka Jiří,
Král Radim,
Vaňková Ilona,
Baliharová Vendula,
Wsól Vladimír
Publication year - 2001
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.10014
Subject(s) - chemistry , stereospecificity , biotransformation , stereoselectivity , enantiomer , diastereomer , stereochemistry , chirality (physics) , in vitro , enzyme , biochemistry , catalysis , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
Flobufen ( F ), a new antiinflammatory drug, has one chiral and one prochiral center in its structure. Reduction of rac ‐ F , the principal biotransformation pathway, leads to the formation of four diastereoisomers of 4‐dihydroflobufen ( DHF ). F was chosen as a model substrate for interspecies comparison of activity, stereospecificity, and stereoselectivity of biotransformation enzymes in fallow bucks, red deer stags, and roe bucks in vitro. Formation of F metabolites was examined in hepatocyte suspension and in subcellular fractions of liver homogenate. (+)‐R ‐F , (−)‐S ‐F and rac ‐ F were used as substrates. After incubation of substrates, the amounts and ratios of DHF diastereoisomers and F enantiomers were assessed by HPLC, with (R,R)‐ULMO and terguride‐bonded columns. Considerable interspecies differences in stereoselectivity and stereospecificity of F reductases were found at the cellular and subcellular levels, although these ruminants are closely related. Chiral inversion of F enantiomers to their antipodes was detected in vitro in all ruminants tested, but individual species also differed in the direction and rate of this inversion. Chirality 13:760–764, 2001. © 2001 Wiley‐Liss, Inc.