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Biomimetic in vitro oxidation of lapachol: a model to predict and analyse the in vivo phase I metabolism of bioactive compounds.

Abstract：

:The bioactive naphtoquinone lapachol was studied in vitro by a biomimetic model with Jacobsen catalyst (manganese(III) salen) and iodosylbenzene as oxidizing agent. Eleven oxidation derivatives were thus identified and two competitive oxidation pathways postulated. Similar to Mn(III) porphyrins, Jacobsen catalyst mainly induced the formation of para-naphtoquinone derivatives of lapachol, but also of two ortho-derivatives. The oxidation products were used to develop a GC-MS (SIM mode) method for the identification of potential phase I metabolites in vivo. Plasma analysis of Wistar rats orally administered with lapachol revealed two metabolites, α-lapachone and dehydro-α-lapachone. Hence, the biomimetic model with a manganese salen complex has evidenced its use as a valuable tool to predict and elucidate the in vivo phase I metabolism of lapachol and possibly also of other bioactive natural compounds.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Niehues M,Barros VP,Emery Fda S,Dias-Baruffi M,Assis Md,Lopes NP

doi

10.1016/j.ejmech.2012.06.042

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

804-12

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(12)00394-7

journal_volume

54

pub_type

杂志文章

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