Characterization of the two major CYP450 metabolites of ozonide (1,2,4-trioxolane) OZ277.
The antimalarial synthetic ozonide OZ277 (RBx11160) was hydroxylated by human liver microsomes at the distal bridgehead carbon atoms of the spiroadamantane substructure to form two carbinol metabolites devoid of antimalarial activity.
Zhou
Lin
L
College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198, USA.
Alker
André
A
Ruf
Armin
A
Wang
Xiaofang
X
Chiu
Francis C K
FC
Morizzi
Julia
J
Charman
Susan A
SA
Charman
William N
WN
Scheurer
Christian
C
Wittlin
Sergio
S
Dong
Yuxiang
Y
Hunziker
Daniel
D
Vennerstrom
Jonathan L
JL
D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D010545:Peroxides / Q000737:chemistry* / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry* / Q000378:metabolism*
C503429:1,2,4-trioxane; D000962:Antimalarials; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; C528887:OZ381; C528886:OZ397; D010545:Peroxides; D013141:Spiro Compounds; C489136:arterolane; D003577:Cytochrome P-450 Enzyme System; D000218:Adamantane