PMID- 29348046
OWN - NLM
STAT- MEDLINE
DCOM- 20180924
LR  - 20180924
IS  - 1873-426X (Electronic)
IS  - 0008-6215 (Linking)
VI  - 457
DP  - 2018 Mar 2
TI  - Synthesis of sulfamide analogues of deoxthymidine monophosphate as potential 
      inhibitors of mycobacterial cell wall biosynthesis.
PG  - 32-40
LID - S0008-6215(17)30858-3 [pii]
LID - 10.1016/j.carres.2018.01.001 [doi]
AB  - The recently discovered enzyme Mycobacterium tuberculosis thymidine monophosphate 
      kinase (TMPKmt), which catalyses the phosphorylation of deoxythymidine 
      monophosphate (dTMP) to give deoxythymidine diphosphate (dTDP), is indispensable 
      for the growth and survival of M. tuberculosis as it plays an essential role in 
      DNA synthesis. Inhibition of TMPKmt is an attractive avenue for the development 
      of novel anti-tuberculosis agents. Based on the premise that sulfamide may be a 
      suitable isostere of phosphate, deoxythymidine analogues comprising various 
      substituted sulfamides at C5' were modelled in silico into the active site of 
      TMPKmt (PDB accession code: 1N5K) using induced-fit docking methods. A selection 
      of modelled compounds was synthesized, and their activity as inhibitors of TMPKmt 
      was evaluated. Three compounds showed competitive inhibition of TMPKmt in the 
      micromolar range (10-50 muM). Compounds were tested in vitro for 
      anti-mycobacterial activity against M. smegmatis: three compounds showed weak 
      anti-mycobacterial activity (MIC 250 mug/mL).
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Suthagar, Kajitha
AU  - Suthagar K
AD  - Department of Chemistry, University of Canterbury, Private Bag 4800, 
      Christchurch, 8140, New Zealand.
FAU - Jiao, Wanting
AU  - Jiao W
AD  - Department of Chemistry, University of Canterbury, Private Bag 4800, 
      Christchurch, 8140, New Zealand; Ferrier Research Institute, Victoria University 
      of Wellington, PO Box 600, Wellington, 6140, New Zealand.
FAU - Munier-Lehmann, Helene
AU  - Munier-Lehmann H
AD  - Institut Pasteur, Unite de Chimie et Biocatalyse, 28 rue du Dr Roux, 75724, Paris 
      Cedex 15, France; CNRS UMR3523, 28 rue du Dr Roux, France.
FAU - Fairbanks, Antony J
AU  - Fairbanks AJ
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20180111
PL  - Netherlands
TA  - Carbohydr Res
JT  - Carbohydrate research
JID - 0043535
RN  - 0 (Antitubercular Agents)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Antitubercular Agents/*chemistry/pharmacology
MH  - Cell Wall/drug effects
MH  - Mycobacterium tuberculosis/drug effects
MH  - Structure-Activity Relationship
MH  - Thymidine/*chemistry/pharmacology
OTO - NOTNLM
OT  - Carbohydrates
OT  - Deoxythymidine
OT  - Mycobacteria
OT  - Sulfamides
OT  - Thymidine monophosphate kinase
OT  - Tuberculosis
EDAT- 2018/01/20 06:00
MHDA- 2018/09/25 06:00
CRDT- 2018/01/20 06:00
PHST- 2017/11/21 00:00 [received]
PHST- 2018/01/08 00:00 [revised]
PHST- 2018/01/08 00:00 [accepted]
PHST- 2018/01/20 06:00 [pubmed]
PHST- 2018/09/25 06:00 [medline]
PHST- 2018/01/20 06:00 [entrez]
AID - S0008-6215(17)30858-3 [pii]
AID - 10.1016/j.carres.2018.01.001 [doi]
PST - ppublish
SO  - Carbohydr Res. 2018 Mar 2;457:32-40. doi: 10.1016/j.carres.2018.01.001. Epub 2018 
      Jan 11.