2. Academic Validation
  3. Synthesis and in vitro evaluation of novel substituted isatin-propylene-1H-1,2,3-triazole-4-methylene-moxifloxacin hybrids for their anti-mycobacterial activities

Synthesis and in vitro evaluation of novel substituted isatin-propylene-1H-1,2,3-triazole-4-methylene-moxifloxacin hybrids for their anti-mycobacterial activities

  • Eur J Med Chem. 2018 Jan 1:143:899-904. doi: 10.1016/j.ejmech.2017.11.090.
Xinjia Yan 1,  Zaosheng Lv 2,  Jing Wen 3,  Shijia Zhao 4,  Zhi Xu 5
Affiliations

Affiliations

  • 1 College of Pharmacy, Harbin University of Commerce, Harbin, Heilongjiang Province 150076, PR China. Electronic address: yanxinjia@yeah.net.
  • 2 Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, Wuhan University of Science and Technology, Hubei, PR China.
  • 3 College of Pharmacy, Harbin University of Commerce, Harbin, Heilongjiang Province 150076, PR China.
  • 4 DXC PharmaTech (Hubei) Co. Ltd., Hubei, PR China.
  • 5 Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, Wuhan University of Science and Technology, Hubei, PR China. Electronic address: chemorgchem@126.com.
PMID: 29227930 DOI: 10.1016/j.ejmech.2017.11.090
Abstract

Twelve novel substituted isatin-propylene-1H-1,2,3-triazole-4-methylene-moxifloxacin hybrids 5a-l were designed, synthesized and screened for their in vitro anti-mycobacterial activities against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis as well as cytotoxicity in VERO cell line. All hybrids exhibited excellent activities against two Mycobacterium tuberculosis strains with minimum inhibitory concentration in the range from 0.05 to 2.0 μg/mL. The most active hybrid 5i was 2-8 times more potent than the reference agents (moxifloxacin and rifampicin) in vitro against Mycobacterium tuberculosis H37Rv, while 2->2048 times more potent than the reference agents (moxifloxacin, rifampicin and isoniazid) in vitro against multidrug-resistant Mycobacterium tuberculosis. However, all hybrids (the 50% cytotoxic concentration/CC50: 2-32 μg/mL) were much more cytotoxic than the parent moxifloxacin (CC50: 128 μg/mL) against VERO cell line. Therefore, our further optimization will focus on their cytotoxicity reducing as well as activity enhancing. The structure-activity relationship of 1H-1,2,3-triazole-tethered isatin-fluoroquinolone hybrids was investigated, and the results could promote further development of the anti-tuberculosis properties of this kind of hybrids.

Keywords

Anti-mycobacterial activity; Isatin; Moxifloxacin; Structure-activity relationship; Triazole.

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