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 Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Li D,Gao N,Zhu N,Lin Y,Li Y,Chen M,You X,Lu Y,Wan K,Jiang JD,Jiang W,Si Sdoi
10.1016/j.bmcl.2015.09.072subject
Has Abstractpub_date
2015-11-15 00:00:00pages
5178-81issue
22eissn
0960-894Xissn
1464-3405pii
S0960-894X(15)30106-2journal_volume
25pub_type
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