Discovery of the disubstituted oxazole analogues as a novel class anti-tuberculotic agents against MDR- and XDR-MTB.

Abstract:

:A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed and synthesized. The newly synthesized compounds 1a-y were evaluated for their in vitro anti-TB activity versus replicating, multi- and extensive drug resistant Mtb strains. All the compounds, except 1o, 1p and 1q, showed potent anti-TB activity with MIC of 1-64 mg/L. The test of broad spectrum panel revealed that this series are specific to Mtb. The cytotoxicity assessment indicated that the compounds were not cytotoxic against HEK 293 cells. The compounds could have a novel mechanism to anti-Mtb as they can inhibit drug sensitive and drug resistant Mtb.

journal_name

Bioorg Med Chem Lett

authors

Li D,Gao N,Zhu N,Lin Y,Li Y,Chen M,You X,Lu Y,Wan K,Jiang JD,Jiang W,Si S

doi

10.1016/j.bmcl.2015.09.072

subject

Has Abstract

pub_date

2015-11-15 00:00:00

pages

5178-81

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)30106-2

journal_volume

25

pub_type

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