Synthesis of arabinose glycosyl sulfamides as potential inhibitors of mycobacterial cell wall biosynthesis

Kajitha Suthagar; Andrew J A Watson; Brendan L Wilkinson; Antony J Fairbanks

doi:10.1016/j.ejmech.2015.07.050

Synthesis of arabinose glycosyl sulfamides as potential inhibitors of mycobacterial cell wall biosynthesis

Eur J Med Chem. 2015 Sep 18:102:153-66. doi: 10.1016/j.ejmech.2015.07.050. Epub 2015 Aug 1.

Authors

Kajitha Suthagar¹, Andrew J A Watson¹, Brendan L Wilkinson², Antony J Fairbanks³

Affiliations

¹ Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand.
² School of Chemistry, Monash University, Box 23, Victoria 3800, Australia.
³ Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand; Biomolecular Interaction Centre, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand. Electronic address: antony.fairbanks@canterbury.ac.nz.

PMID: 26263247
DOI: 10.1016/j.ejmech.2015.07.050

Abstract

A series of arabinose glycosyl sulfamides with varying alkyl chain types and lengths were synthesised as mimics of decaprenolphosphoarabinose (DPA), and as potential inhibitors of mycobacterial cell wall biosynthesis. Unprecedented conversion of the desired furanose to the thermodynamically more stable pyranose form occurred during final de-protection. Biological testing against Mycobacterium smegmatis revealed low to moderate anti-mycobacterial activity with marked dependence on alkyl chain length, which in the case of mono-substituted sulfamides was maximal for a C-10 chain.

Keywords: Arabinose; Carbohydrates; Furanosides; Mycobacteria; Pyranosides; Sulfamides; Tuberculosis.

Publication types

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

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Arabinose / chemistry
Arabinose / pharmacology*
Cell Wall / drug effects*
Cell Wall / metabolism
Dose-Response Relationship, Drug
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium smegmatis / cytology*
Mycobacterium smegmatis / drug effects*
Mycobacterium smegmatis / metabolism
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Anti-Bacterial Agents
Sulfonamides
Arabinose