Synthesis and antitubercular and antibacterial activity of some active fluorine containing quinoline–pyrazole hybrid derivatives
| Autor: | Nagabhushana Nayak, Jurupula Ramprasad, Udayakumar Dalimba |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
chemistry.chemical_classification
biology 010405 organic chemistry Stereochemistry INHA Organic Chemistry Quinoline Pyrazole 010402 general chemistry biology.organism_classification 01 natural sciences Biochemistry In vitro 0104 chemical sciences Inorganic Chemistry Mycobacterium tuberculosis chemistry.chemical_compound Enzyme chemistry Environmental Chemistry Physical and Theoretical Chemistry Cytotoxicity Antibacterial activity |
| Zdroj: | Journal of Fluorine Chemistry. 183:59-68 |
| ISSN: | 0022-1139 |
| DOI: | 10.1016/j.jfluchem.2016.01.011 |
| Popis: | In an attempt to develop newer antitubercular and antibacterial agents against the increasing bacterial resistance, we have designed new quinoline–pyrazole analogs ( 8a – u ) following the molecular hybridization approach. The structure of one of the final compounds, 8a was unambiguously confirmed by single crystal X-ray diffraction (SC-XRD) analysis. The target compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis and antibacterial activity against three common pathogenic bacterial strains. Four derivatives ( 8b , 8c , 8j and 8o ) displayed significant antitubercular activity. The compounds derived from 8-trifluoromethylquinoline and 6-fluoroquinoline scaffolds with halogen substitution on the pyrazole ring exhibited superior inhibition activity than corresponding 6-methoxyquinoline analogs. The cytotoxic studies revealed that the active compounds are nontoxic to normal Vero cell lines with selectivity index values ≥10, which indicate the suitability of these compounds for further drug development. The in silico molecular docking study demonstrated strong binding affinity of the compounds with the target enzymes (InhA, CYP121 and TMPK) of M. tuberculosis . Further, the in vitro antibacterial activity of compounds 8b, 8c, 8d and 8g is comparable with that of the reference drug, Ciprofloxacin. |
| Databáze: | OpenAIRE |
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