PMID- 29784273
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20190528
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 26
IP  - 19
DP  - 2018 Oct 15
TI  - Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus 
      therapeutics.
PG  - 5343-5348
LID - S0968-0896(18)30423-1 [pii]
LID - 10.1016/j.bmc.2018.05.019 [doi]
AB  - Incorporation of halogen atoms to drug molecule has been shown to improve its 
      properties such as enhanced in membrane permeability and increased hydrophobic 
      interactions to its target. To investigate the effect of halogen substitutions on 
      the antibacterial activity of trimethoprim (TMP), we synthesized a series of 
      halogen substituted TMP and tested for their antibacterial activities against 
      global predominant methicillin resistant Staphylococcus aureus (MRSA) strains. 
      Structure-activity relationship analysis suggested a trend in potency that 
      correlated with the ability of the halogen atom to facilitate in hydrophobic 
      interaction to saDHFR. The most potent derivative, iodinated trimethoprim 
      (TMP-I), inhibited pathogenic bacterial growth with MIC as low as 1.25 mug/mL 
      while the clinically used TMP derivative, diaveridine, showed resistance. Similar 
      to TMP, synergistic studies indicated that TMP-I functioned synergistically with 
      sulfamethoxazole. The simplicity in the synthesis from an inexpensive starting 
      material, vanillin, highlighted the potential of TMP-I as antibacterial agent for 
      MRSA infections.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Nilchan, Napon
AU  - Nilchan N
AD  - Department of Chemistry and Center for Innovation in Chemistry (PERCH-CIC), 
      Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
FAU - Phetsang, Wanida
AU  - Phetsang W
AD  - Department of Chemistry and Center for Innovation in Chemistry (PERCH-CIC), 
      Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
FAU - Nowwarat, Taechin
AU  - Nowwarat T
AD  - Department of Chemistry and Center for Innovation in Chemistry (PERCH-CIC), 
      Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
FAU - Chaturongakul, Soraya
AU  - Chaturongakul S
AD  - Department of Microbiology, Faculty of Science, Mahidol University, Rama VI Road, 
      Bangkok 10400, Thailand; Center for Emerging Bacterial Infections, Faculty of 
      Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
FAU - Jiarpinitnun, Chutima
AU  - Jiarpinitnun C
AD  - Department of Chemistry and Center for Innovation in Chemistry (PERCH-CIC), 
      Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. 
      Electronic address: chutima.jia@mahidol.ac.th.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180519
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Anti-Bacterial Agents)
RN  - AN164J8Y0X (Trimethoprim)
RN  - JE42381TNV (Sulfamethoxazole)
SB  - IM
MH  - Anti-Bacterial Agents/chemical synthesis/*chemistry/pharmacology
MH  - Drug Synergism
MH  - Halogenation
MH  - Methicillin-Resistant Staphylococcus aureus/drug effects
MH  - Microbial Sensitivity Tests
MH  - Structure-Activity Relationship
MH  - Sulfamethoxazole/pharmacology
MH  - Trimethoprim/analogs & derivatives/*chemical synthesis/pharmacology
OTO - NOTNLM
OT  - Halogenation
OT  - Methicillin resistant Staphylococcus aureus
OT  - Trimethoprim
EDAT- 2018/05/23 06:00
MHDA- 2019/05/29 06:00
CRDT- 2018/05/23 06:00
PHST- 2018/02/28 00:00 [received]
PHST- 2018/05/10 00:00 [revised]
PHST- 2018/05/13 00:00 [accepted]
PHST- 2018/05/23 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2018/05/23 06:00 [entrez]
AID - S0968-0896(18)30423-1 [pii]
AID - 10.1016/j.bmc.2018.05.019 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2018 Oct 15;26(19):5343-5348. doi: 10.1016/j.bmc.2018.05.019. 
      Epub 2018 May 19.