Design, synthesis, and biological evaluation of novel benzimidazole tethered allylidenehydrazinylmethylthiazole derivatives as potent inhibitors of .

Journal: MedChemComm
Published Date:

Abstract

Tuberculosis (TB) has become one of the most significant public health problems in recent years. Antibiotic therapy remains the mainstay of TB control strategies, but the increasing resistance of mycobacterial species has heightened alarm, requiring the development of novel drugs in order to improve treatment outcomes. Here, as an effort to identify novel and effective antitubercular agents, we designed and synthesized a series of novel substituted benzimidazolallylidenehydrazinylmethylthiazole derivatives a multi-component molecular hybridization approach with single molecular architecture. Our design strategy involved assembling the antitubercular pharmacophoric fragments benzimidazole, 2-aminothiazole and substituted α,β-unsaturated ketones condensation reactions. All the newly synthesized compounds were fully characterized NMR and mass spectral data and evaluated for biological activity against the H37Ra strain of . From the biological evaluation data, we identified some effective compounds, of which and were the most active ones (both having MIC values of 2.5 μg mL). In addition, compound exhibited a lower cytotoxicity profile. We conceive that compound may serve as a chemical probe of interest for further lead optimization studies with the general aim of developing novel and effective antitubercular agents.

Authors

  • Goverdhan Surineni
    State Key Laboratory of Respiratory Disease , Guangzhou Institutes of Biomedicine and Health (GIBH) , Chinese Academy of Sciences (CAS) , Guangzhou-510530 , China . Email: zhang_tianyu@gibh.ac.cn ; ; Tel: (+86)20 3201 5270.
  • Yamin Gao
    State Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
  • Muzammal Hussain
    State Key Laboratory of Respiratory Disease , Guangzhou Institutes of Biomedicine and Health (GIBH) , Chinese Academy of Sciences (CAS) , Guangzhou-510530 , China . Email: zhang_tianyu@gibh.ac.cn ; ; Tel: (+86)20 3201 5270.
  • Zhiyong Liu
    State Key Laboratory of Respiratory Disease , Guangzhou Institutes of Biomedicine and Health (GIBH) , Chinese Academy of Sciences (CAS) , Guangzhou-510530 , China . Email: zhang_tianyu@gibh.ac.cn ; ; Tel: (+86)20 3201 5270.
  • Zhili Lu
    State Key Laboratory of Respiratory Disease , Guangzhou Institutes of Biomedicine and Health (GIBH) , Chinese Academy of Sciences (CAS) , Guangzhou-510530 , China . Email: zhang_tianyu@gibh.ac.cn ; ; Tel: (+86)20 3201 5270.
  • Chiranjibi Chhotaray
    State Key Laboratory of Respiratory Disease , Guangzhou Institutes of Biomedicine and Health (GIBH) , Chinese Academy of Sciences (CAS) , Guangzhou-510530 , China . Email: zhang_tianyu@gibh.ac.cn ; ; Tel: (+86)20 3201 5270.
  • Md Mahmudul Islam
    State Key Laboratory of Respiratory Disease , Guangzhou Institutes of Biomedicine and Health (GIBH) , Chinese Academy of Sciences (CAS) , Guangzhou-510530 , China . Email: zhang_tianyu@gibh.ac.cn ; ; Tel: (+86)20 3201 5270.
  • H M Adnan Hameed
    State Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
  • Tianyu Zhang
    State Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.

Keywords

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