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International Journal of Medicinal Chemistry
Volume 2016, Article ID 3475235, 6 pages
http://dx.doi.org/10.1155/2016/3475235
Research Article

Synthesis and Evaluation of Mannitol-Based Inhibitors for Lipopolysaccharide Biosynthesis

Centre for Analysis and Synthesis, Lund University, P.O. Box 124, 221 00 Lund, Sweden

Received 8 November 2015; Revised 6 January 2016; Accepted 17 January 2016

Academic Editor: Patrick J. Bednarski

Copyright © 2016 Richard E. Johnsson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Antibiotic resistance is a serious threat against humankind and the need for new therapeutics is crucial. Without working antibiotics, diseases that we thought were extinct will come back. In this paper two new mannitol bisphosphate analogs, 1,6-dideoxy-1,6-diphosphoramidate mannitol and 1,6-dideoxy-1,6-dimethansulfonamide mannitol, have been synthesized and evaluated as potential inhibitors of the enzyme GmhB in the biosynthesis of lipopolysaccharides. 1,6-Dideoxy-1,6-diphosphoramidate mannitol showed promising result in computational docking experiments, but neither phosphate analog showed activity in the Kirby-Bauer antibiotic susceptibility test.