Biomimetic oxidation of praziquantel catalysed by metalloporphynins

This paper reports an RPLC-MS/MS investigation of praziquantel (anthelmintic agent) oxidation by iodosylbenzene in an organic medium. using iron(III) tetraarylporphyrins (where aryl = phenyl, pentafluorophenyl, 2-nitrophenyl, 2-trifluoromethylphenyl and mesityl) and manganese(III) tetrapherylporphyrin as catalysts. The majority of the oxidation products have been identified by sequential MS and NMR analyses. The selectivities of the oxidations by these cytochrome, P-450 models are studied and compared. Time dependent reaction profiles suggest that with all the catalysts, the initial oxidation occurs predominantly at the 7-position. With Fe(T2TFMPP)Cl the yield and selectivity (64%) for 7-hydroxypraziquantel remain high even after 24 h reaction, whereas with the other catalysts this initial product is further oxidized to di- and trihydroxypraziquantel. The Fe(TFPP)Cl system results in the higher yield (11%) of cis- and trans-4'-hydroxypraziquantel the major metabolites from in vivo and in vitro metabolism of praziquantel by cytochrome P-450 monooxygenases. (C) 2004 Elsevier B.V. All rights reserved.