| Title : Synthesis and evaluation of esters and carbamates to identify critical functional groups for esterase-specific metabolism - Yoon_2003_Bioorg.Med.Chem_11_3237 |
| Author(s) : Yoon KJ , Morton CL , Potter PM , Danks MK , Lee RE |
| Ref : Bioorganic & Medicinal Chemistry , 11 :3237 , 2003 |
|
Abstract :
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. |
| PubMedSearch : Yoon_2003_Bioorg.Med.Chem_11_3237 |
| PubMedID: 12837533 |
Yoon KJ, Morton CL, Potter PM, Danks MK, Lee RE (2003)
Synthesis and evaluation of esters and carbamates to identify critical functional groups for esterase-specific metabolism
Bioorganic & Medicinal Chemistry
11 :3237
Yoon KJ, Morton CL, Potter PM, Danks MK, Lee RE (2003)
Bioorganic & Medicinal Chemistry
11 :3237