Background: E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2
(Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin
analogues, modified deoxycholic acid at 20-position of CPT(camptothecin) with greater
anticancer activity and lower systematic toxicity in vivo.
Objective: We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes
Methods: Phase I and Phase II metabolism of E2 and G2 in rat liver microsomes were performed,
respectively, and the mixed incubation of phase I and phase II metabolism of E2 and G2 was also
processed. Metabolites were identified by liquid chromatographic/mass spectrometry.
Results: The results showed that phase I metabolism was the major biotransformation route for
both E2 and G2. The isoenzyme involved in their metabolism had some difference. The intrinsic
clearance of G2 was 174.7 mL/min. mg protein, more than three times that of E2 (51.3 mL/min .
mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites
of G2 were detected, including phase I metabolites (mainly via hydroxylations and hydrolysis)
and their further glucuronidation products.
Conclusion: These findings suggested that E2 and G2 have similar biotransformation pathways except
for some differences in the hydrolysis ability of the ester bond and amino bond from the parent
compounds, which may result in the diversity of their metabolism stability and responsible
CYPs(Cytochrome P450 proteins).