Biomimetic in vitro oxidation of lapachol: a model to predict and analyse the in vivo phase I metabolism of bioactive compounds.
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.
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Cafe S/N, 14040-903 Ribeirao Preto, SP, Brazil.
Michael
M
Niehues
Valéria Priscila
VP
Barros
Flávio da Silva
Fda S
Emery
Marcelo
M
Dias-Baruffi
Marilda das Dores
Md
Assis
Norberto Peporine
NP
Lopes
D000818:Animals; D032701:Biomimetics / Q000379:methods*; D005029:Ethylenediamines / Q000737:chemistry; D005260:Female; D008954:Models, Biological; D009285:Naphthoquinones / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D005029:Ethylenediamines; D009285:Naphthoquinones; D009942:Organometallic Compounds; D016877:Oxidants; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); C008252:lapachol