2. Academic Validation
  3. Design and synthesis of biaryloxazolidinone derivatives containing a rhodanine or thiohydantoin moiety as novel antibacterial agents against Gram-positive bacteria

Design and synthesis of biaryloxazolidinone derivatives containing a rhodanine or thiohydantoin moiety as novel antibacterial agents against Gram-positive bacteria

  • Bioorg Med Chem Lett. 2019 Feb 1;29(3):496-502. doi: 10.1016/j.bmcl.2018.12.012.
Yachuang Wu 1,  Xiudong Ding 2,  Sicong Xu 1,  Yifeng Yang 1,  Xue Zhang 1,  Chu Wang 2,  Hong Lei 3,  Yanfang Zhao 4
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
  • 2 Department of Clinical Laboratory, The 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
  • 3 Department of Clinical Laboratory, The 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China. Electronic address: jlh309@163.com.
  • 4 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: yanfangzhao@syphu.edu.cn.
PMID: 30553735 DOI: 10.1016/j.bmcl.2018.12.012
Abstract

Novel biaryloxazolidinone derivatives containing a rhodanine or thiohydantoin moiety were designed, synthesized and evaluated for their Antibacterial activity. The key compounds 7 and 9 were synthesized by the knoevenagel condensation of intermediate aldehyde 5 with rhodanine derivatives 6a-6b. The preliminary study showed that compounds 7, 9 and 10e exhibited potent Antibacterial activity with MIC values of 0.125 µg/mL against S. aureus, MRSA, MSSA, LREF and VRE pathogens, using linezolid and radezolid as the positive controls. The most promising compound 10e exhibited potent Antibacterial activity against tested clinical isolates of MRSA, MSSA, VRE and LREF with MIC values in the range of 0.125-0.5 µg/mL, and the potency of 10e against clinical isolates of LREF was 64-fold higher than that of linezolid. Moreover, compound 10e was non-cytotoxic with an IC50 value of 91.04 μM against HepG2 cell. Together, compound 10e might serve as a novel Antibacterial agent for further investigation.

Keywords

Antibacterial activity; Biaryloxazolidinone; Gram-positive bacteria; Rhodanine derivatives.

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