Synthesis and evaluation of esters and carbamates to identify critical functional groups for esterase-specific metabolism

Bioorg Med Chem. 2003 Jul 31;11(15):3237-44. doi: 10.1016/s0968-0896(03)00302-x.


In an effort to develop novel prodrugs for viral directed enzyme prodrug therapy (VDEPT) approaches to chemotherapy, eleven esters and carbamates of o-nitrophenol, p-nitrophenol, and beta-naphthol were synthesized and characterized as substrates for rabbit (rCE) and human liver (hCE1) carboxylesterases. All of the esters of o-, p-nitrophenols, and beta-naphthols showed moderate hydrolysis by both rCE and hCE1. Esters of beta-naphthols exhibited higher hydrolysis rates compared to esters of p-nitrophenols by rCE. Of the carbamates, 4-benzyl-piperazine-1-carboxylic acid 2-nitrophenol showed preferential hydrolysis by rCE compared to hCE1 with a V(max) of 54.4 micromoles/min/mg, and a K(m) value of 1071 microM. Substrate metabolism by a specific CE or inhibition of CEs by each compound depended on several factors, including the types of functional groups and linking moieties.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbamates / chemical synthesis*
  • Carbamates / metabolism*
  • Drug Evaluation, Preclinical / methods
  • Esterases / metabolism*
  • Esters
  • Humans
  • Rabbits


  • Carbamates
  • Esters
  • Esterases