Background: The activation or overexpression of histone deacetylases (HDACs) are associated
with the development of numerous cancers. The importance of HDACs in new anticancer
therapeutic strategies has led researchers to develop promising anticancer drugs, design, and synthesis
of novel HDACs inhibitors are also in progress. E14 was synthesized and acted as a selective inhibitor
of HDACs I.
Methods: We develop a sensitive UPLC-QTOF-MS/MS method to discover the new phase I and II
metabolites of E14 from complex biological matrices in plasma, feces, and urine of rats. Then a
strategy comparing samples after administration with blank samples was applied to distinguish
metabolites. The accurate measurements of the product ions obtained by high-resolution mass spectrometry,
the structure of the parent drug and its detected metabolites are used to verify its fragmentation
pathway and to obtain the proposed structure of the metabolites.
Results: Fourteen metabolites were tentatively identified, including twelve metabolites in urine,
five in plasma and one metabolite in feces. Hydroxylation, oxidation, methylation, N-demethylation,
dehydration, glucuronidation, dehydroxylation and hydrolysis were the main metabolic pathways
Conclusion: E14 is a drug with a variety of metabolites and metabolic pathways. E14 metabolites
was excreted most in urine, indicating the main metabolic organ was the kidney.