Design, synthesis, and evaluation of potential prodrugs of DFMO for reductive activation

Yanhui Yang; Andrew Voak; Shane R Wilkinson; Longqin Hu

doi:10.1016/j.bmcl.2012.09.005

Design, synthesis, and evaluation of potential prodrugs of DFMO for reductive activation

Bioorg Med Chem Lett. 2012 Nov 1;22(21):6583-6. doi: 10.1016/j.bmcl.2012.09.005. Epub 2012 Sep 13.

Authors

Yanhui Yang¹, Andrew Voak, Shane R Wilkinson, Longqin Hu

Affiliation

¹ Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

PMID: 23031595
DOI: 10.1016/j.bmcl.2012.09.005

Abstract

A series of potential DFMO prodrugs was designed through the incorporation of 4-nitrobenzyl ester or carbamate groups for potential activation by trypanosomal nitroreductase. It was found that only modification of N(ε)-amino group of DFMO by 4-nitro-2-fluorobenzyloxycarbonyl resulted in significant trypanocidal activity and could serve as a lead for further investigation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Drug Design*
Models, Biological
Nitroreductases / metabolism
Oxidation-Reduction
Prodrugs / chemical synthesis
Prodrugs / chemistry*
Prodrugs / pharmacology*
Trypanocidal Agents / chemical synthesis
Trypanocidal Agents / chemistry*
Trypanocidal Agents / pharmacology*
Trypanosoma / drug effects*
Trypanosoma / enzymology

Substances

Prodrugs
Trypanocidal Agents
Nitroreductases