Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance work on Wednesday 27th March 2019 from 11:00 AM to 1:00 PM (GMT).

During this time our website performance may be temporarily affected. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 32, 2013
Previous Article Next Article

Discovery of N-(4-sulfamoylphenyl)thioureas as Trypanosoma brucei leucyl-tRNA synthetase inhibitors

Author affiliations

Abstract

Human African trypanosomiasis (HAT) is one of the most neglected diseases in the tropic regions, which is fatal if not treated in time. There is an urgent need for new therapeutics, especially those in new chemical classes. Leucyl-tRNA synthetase (LeuRS) has been paid much attention as a recently clinically validated antimicrobial target. Our group has previously reported T. brucei LeuRS (TbLeuRS) inhibitors, including benzoxaboroles targeting the editing site and pyrrolinones targeting the synthetic site. Here we report the discovery of N-(4-sulfamoylphenyl)thioureas as a new class of TbLeuRS inhibitors. The R1 and R2 groups, reminiscent of the leucyl and adenyl regions of aa-AMP and aa-AMS, were optimized to result in a significant 13-fold increase of inhibitory activity (compound 19, IC50 = 13.7 μM). Aided by ligandprotein docking, the 1,3-substitution at the central phenyl ring was predicted and proved to give significantly improved activity (59, IC50 = 1.1 μM). This work provided a new scaffold for the exploration of novel inhibitors against TbLeuRS, which may become potential therapeutics for the treatment of HAT.

Graphical abstract: Discovery of N-(4-sulfamoylphenyl)thioureas as Trypanosoma brucei leucyl-tRNA synthetase inhibitors

Back to tab navigation

Publication details

The article was received on 01 Feb 2013, accepted on 18 Jun 2013 and first published on 19 Jun 2013


Article type: Paper
DOI: 10.1039/C3OB40236C
Citation: Org. Biomol. Chem., 2013,11, 5310-5324

  •   Request permissions

    Discovery of N-(4-sulfamoylphenyl)thioureas as Trypanosoma brucei leucyl-tRNA synthetase inhibitors

    F. Zhang, J. Du, Q. Wang, Q. Hu, J. Zhang, D. Ding, Y. Zhao, F. Yang, E. Wang and H. Zhou, Org. Biomol. Chem., 2013, 11, 5310
    DOI: 10.1039/C3OB40236C

Search articles by author

Spotlight

Advertisements