Абстрактный

Study of metabolism of diclofenac-using microbial cultures

M.Vidyavathi, K.V.S.R.G. Prasad, D.R.Krishna

To develop a microbial model for study of metabolism of diclofenac for further pharmacological and toxicological studies and to produce the metabolites which are difficult for chemical synthesis due to many steps and requirement of regio , stereo specificity. The metabolites of diclofenac in microbial cultures were identified and confirmed using fermentation techniques, HPLC and LCMS methods. Among different organisms screened Pseudomonas aeruginosa and Cunninghmella elegans showed extra peaks at 5, 8.6 and 8.5m. Respectively inHPLC indicating formation ofmetabolite by these two micro organisms. The metabolites were characterized by Liquid Chromatography Mass Spectrometry and were found as methoxy, hydroxy diclofenac formed by Pseudomonas aeruginosa and as dihydroxy diclofenac formed by Cunninghmella elegans which were similar to mammalian CYP 2C9mediated hydroxy diclofenac and other minormammalian metabolitemethoxy hydroxy diclofenac. Thus, the above twomicrobeswere able tometabolize diclofenac asmammalian CYP 2C9mediated oxidation . The present study demonstrates a microbial model to produce CYP 2C9 mediated metabolites of diclofenac using simple, easy fermentation technique.