Abstract：
:Mycobacterium tuberculosis, the causative agent of tuberculosis, has surpassed HIV as the leading cause of death due to an infectious disease worldwide, being responsible for more than 1.5 million deaths in low-income countries. In response to a pandemic threat by drug resistant strains, the tuberculosis research community is searching for new chemical entities with novel mechanisms of action to avoid drug resistance and shorten treatment regimens using combinatorial chemotherapy. Herein, we have identified several novel chemical scaffolds, GSK97C (spiro-oxazolidin-2-one), GSK93A (2-amino-1,3-thiazole, GSK85A and GSK92A (enamides), which target M. tuberculosis aspartyl-tRNA synthetase (Mt-AspRS), an essential component of the protein synthesis machinery of tuberculosis, using a whole-cell target-based screening strategy against a genetically modified Mycobacterium bovis BCG strain. We also provide further evidence of protein inhibition and inhibitor profiling through a classical aminoacylation reaction and a tRNA-independent assay, respectively. Altogether, our results have identified a number of hit new molecules with novel mechanism of action for further development through medicinal chemistry as hits and leads.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Soto R,Perez-Herran E,Rodriguez B,Duma BM,Cacho-Izquierdo M,Mendoza-Losana A,Lelievre J,Aguirre DB,Ballell L,Cox LR,Alderwick LJ,Besra GSdoi
10.1038/s41598-018-31157-3subject
Has Abstractpub_date
2018-08-23 00:00:00pages
12664issue
1issn
2045-2322pii
10.1038/s41598-018-31157-3journal_volume
8pub_type
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journal_title：Scientific reports
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