Can I read Design, synthesis, and evaluation of potential carbamate prodrugs of 5′-methylthioadenosine (MTA) on EtoBox?

Design, synthesis, and evaluation of potential carbamate prodrugs of 5′-methylthioadenosine (MTA) by Ashwini Sadanand Ranade; Joseph R. Bertino; Longqin Hu is a Chemistry article available to read on EtoBox.

What is Design, synthesis, and evaluation of potential carbamate prodrugs of 5′-methylthioadenosine (MTA) about?

5′-Methylthioadenosine (MTA) is a natural substrate of MTA phosphorylase (MTAP) and is converted to adenine via a salvage pathway for AMP production in normal healthy cells. The lack of MTAP expression in many solid tumors and hematologic malignancies compared to normal healthy cells has been explored in a potential therapeutic strategy to selectively target tumor cells using antimetabolites such as 5-fluorouracil (5-FU) and 6-thioguanine (6-TG) while protecting normal healthy cells with MTA. Herein, a series of carbamate prodrugs, namely the N-(alkyloxy)carbonyl-MTA derivatives 2a-f, was designed, synthesized, and evaluated as potential prodrugs of MTA. All carbamate prodrugs were stable in phosphate buffer, pH 7.4 at 37 °C. In the presence of mouse liver microsomes, the prodrugs were converted to MTA at varying rates with the hexyl and butyl carbamates 2a and 2b most readily activated (t 1/2 of 1.2 and 9.4 h, respectively). The activation was shown to be mediated by carboxyesterases present in mouse liver microsomes.

Who reads Design, synthesis, and evaluation of potential carbamate prodrugs of 5′-methylthioadenosine (MTA)?

Author

Ashwini Sadanand Ranade; Joseph R. Bertino; Longqin Hu

Publisher

Springer Science and Business Media LLC

Published

2021

Language

EN

Field

Chemistry (Physical Sciences)