Synthesis and in vitro evaluation of novel substituted isatin-propylene-1H-1,2,3-triazole-4-methylene-moxifloxacin hybrids for their anti-mycobacterial activities
| Autor: | Zhi Xu, Xinjia Yan, Zaosheng Lv, Shi‐Jia Zhao, Jing Wen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Isatin
Cell Survival Moxifloxacin Microbial Sensitivity Tests Alkenes 010402 general chemistry 01 natural sciences Microbiology Mycobacterium tuberculosis Mice Structure-Activity Relationship Minimum inhibitory concentration chemistry.chemical_compound Chlorocebus aethiops Tuberculosis Multidrug-Resistant Drug Discovery medicine Animals Cytotoxicity Vero Cells Pharmacology Mice Inbred ICR Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Chemistry Organic Chemistry Isoniazid General Medicine Triazoles biology.organism_classification Anti-Bacterial Agents 0104 chemical sciences Vero cell Female Rifampicin Fluoroquinolones medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 143:899-904 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2017.11.090 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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