ABSTRACT
We describe in this work the synthesis of nine new fluoroquinolone derivatives based on modifications at the C-7 position of the known fluoroquinolones cipro-, gati-, and moxifloxacin, as well as their antitubercular evaluation. The synthesis of these new analogues was improved using microwave irradiation, providing several advantages such as better yields and shorter reaction times, in comparison with classical reaction conditions. Derivatives 4, 5, and 7 exhibited promising antitubercular activities.
Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Carbohydrates/chemistry , Fluoroquinolones/chemical synthesis , Fluoroquinolones/pharmacology , Antitubercular Agents/chemistry , Aza Compounds/chemistry , Aza Compounds/pharmacology , Ciprofloxacin/chemistry , Ciprofloxacin/pharmacology , Fluoroquinolones/chemistry , Gatifloxacin , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Structure , Moxifloxacin , Mycobacterium tuberculosis/drug effects , Quinolines/chemistry , Quinolines/pharmacologyABSTRACT
We report in this work the antibacterial evaluation of 12 lipophilic fluoroquinolone derivatives containing diaminoalkyl side chains at C-7 position. The compounds were investigated against 15 bacterial strains including gram-negative and gram-positive species of clinical and microbiological importance. Three compounds (5, 10 and 11) were as active as or more efficient than gatifloxacin against gram-positive bacteria M. lentus. When compared with gatifloxacin compound 10 was 16 times more active. Two compounds (11 and 12) were twice more active than the reference compound against S. aureus.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Fluoroquinolones/chemistry , Fluoroquinolones/pharmacology , Hydrophobic and Hydrophilic Interactions , Anti-Bacterial Agents/chemical synthesis , Aza Compounds/chemistry , Fluoroquinolones/chemical synthesis , Gatifloxacin , Microbial Sensitivity Tests , Moxifloxacin , Quinolines/chemistryABSTRACT
The fluoroquinolones are an important family of synthetic antimicrobial agents being clinically used over the past thirty years. In addition, some fluoroquinolones have been used in the development of anticancer drugs, and others have demonstrated anti-HIV activity. Furthermore, there has been some additional work investigating the effect of metal ions on biological activity. Aiming to obtain novel palladium(II) and platinum(II) complexes that exhibit biological activity, we have synthesized complexes using fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin, and gatifloxacin) as ligands. The compounds were characterized using IR and NMR spectroscopy, thermogravimetric and elemental analyses. The complexes show activity against Mycobacterium tuberculosis strain H(37)Rv. The minimal inhibitory concentration (MIC) of the complexes was determined.
Subject(s)
Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Fluoroquinolones/chemistry , Fluoroquinolones/pharmacology , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/pharmacology , Platinum/chemistry , Platinum/pharmacology , Antitubercular Agents/chemical synthesis , Fluoroquinolones/chemical synthesis , Mycobacterium tuberculosis/drug effects , Organoplatinum Compounds/chemical synthesis , Structure-Activity RelationshipABSTRACT
Fluoroquinolone (FQ) has a broad spectrum of activity against several bacteria, mycobacteria, parasites, and other diseases. Moxifloxacin and gatifloxacin are a new generation of fluoroquinolone agents with improved activity against Gram-negative and positive bacteria. As lipophilicity is an important consideration in the design and activity of novel antibacterial agents, we report in this work the synthesis and biological evaluation of 12 lipophilic moxifloxacin or gatifloxacin derivatives, by reaction of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid 13 with several N-monoalkyl 1,2-ethanediamine or 1,3-propanediamine.
Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Aza Compounds/chemistry , Aza Compounds/pharmacology , Fluoroquinolones/chemistry , Fluoroquinolones/pharmacology , Lipids/chemistry , Quinolines/chemistry , Quinolines/pharmacology , Antitubercular Agents/chemistry , Aza Compounds/chemical synthesis , Fluoroquinolones/chemical synthesis , Gatifloxacin , Molecular Structure , Moxifloxacin , Quinolines/chemical synthesis , Streptococcus pneumoniae/drug effects , Structure-Activity RelationshipABSTRACT
The structure-activity relationships (SAR) of new antibacterial benzenesulfonamidefluoroquinolones (BSFQs), coming from derivatization of N4-piperazinyl of ciprofloxacin (CIP) were studied. The behavior of the new BSFQ series was similar to the previously norfloxacin (NOR) analogs reported, making possible a quantitative structure-activity relationships (QSAR) analysis of the complete set of BSFQs. The presence of the benzenesulfonylamido (BS) groups shifted the activity of classic antimicrobial fluoroquinolones from being more active against Gram-negative to Gram-positive strains. QSAR studies through Hansch analysis showed a linear correlation of the activity with electronic and steric parameters. Small electron-donor groups would increase the in vitro activity against Gram-positive bacteria. Hydrophobic properties played a minor role when activity is measured as minimum inhibitory concentration (MIC). QSAR analysis also reinforces previous biological findings about the presence of new interactions with target topoisomerases.