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Bioorg Med Chem. 2013 Apr 15;21(8):2286-2297. doi: 10.1016/j.bmc.2013.02.008. Epub 2013 Feb 19.

Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents.

Author information

1
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, P. R. China.
2
School of Pharmacy, Second Military Medical University, Shanghai 200433, P. R. China. Electronic address: wqzhong2002@sohu.com.
3
Xuzhou Central Hospital, Xuzhou 221009, P. R. China. Electronic address: ghbxzh@yahoo.com.cn.
4
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, P. R. China. Electronic address: zhuhl@nju.edu.cn.

Abstract

A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7±0.2, 30.0±1.2, 18.3±1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56-3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study.

PMID:
23490159
DOI:
10.1016/j.bmc.2013.02.008
[Indexed for MEDLINE]

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