2. Academic Validation
  3. Benzofuran-isatin hybrids and their in vitro anti-mycobacterial activities against multi-drug resistant Mycobacterium tuberculosis

Benzofuran-isatin hybrids and their in vitro anti-mycobacterial activities against multi-drug resistant Mycobacterium tuberculosis

  • Eur J Med Chem. 2019 Dec 1:183:111678. doi: 10.1016/j.ejmech.2019.111678.
Feng Gao 1,  Lei Ye 2,  Yabin Wang 2,  Fangong Kong 2,  Shijia Zhao 3,  Jiaqi Xiao 4,  Gang Huang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology (Shandong Academy of Sciences), Jinan, PR China; Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, PR China. Electronic address: rggaofeng@hotmail.com.
  • 2 State Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology (Shandong Academy of Sciences), Jinan, PR China.
  • 3 Wuhan University of Science and Technology, Wuhan, Hubei, PR China.
  • 4 State Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology (Shandong Academy of Sciences), Jinan, PR China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, PR China. Electronic address: jiaqixiao@qlu.edu.cn.
  • 5 Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, PR China. Electronic address: huanggang@sumhs.edu.cn.
PMID: 31525660 DOI: 10.1016/j.ejmech.2019.111678
Abstract

A series of benzofuran-isatin hybrids 6a-n and 7a-g linked by alkyl linkers were designed and synthesized. Among them, hybrids 6a-l and 7a-g were assessed for their in vitro anti-mycobacterial activities against two multi-drug resistant Mycobacterium tuberculosis (MDR-MTB) strains and the cytotoxicity towards CHO cells. The preliminary results indicated that all hybrids (MIC: 0.125-16 μg/mL) showed excellent activity against the tested MDR-MTB strains, and low cytotoxicity (CC50: 64->512 μg/mL) towards CHO cells. Among them, hybrid 7e (MIC: 0.125 and 0.25 μg/mL) was highly active against the tested two MDR-MTB strains, which was 8-16 folds better than ciprofloxacin (MIC: 1 and 4 μg/mL), ≥512 folds more potent than rifampicin (MIC: 64 and > 128 μg/mL) and isoniazid (MIC: >128 μg/mL), but it was less active than TAM16 (MIC: <0.06 μg/mL). Moreover, the hybrid 7e (CC50: 128 μg/mL) also showed low cytotoxicity towards CHO cells, and high selectivity index (1,024). However, the metabolic stability and in vivo pharmacokinetic profiles of hybrid 7e were inferior to TAM16, so it still needs to be modified so as to get the optimized hybrid for potential use in mycobacterial treatment.

Keywords

Benzofuran; Isatin; Multi-drug resistant Mycobacterium tuberculosis; Structure-activity relationship.

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