Synthesis, in vitro and in vivo antimycobacterial activities of diclofenac acid hydrazones and amides

Various diclofenac acid hydrazones and amides were synthesized and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis. Preliminary results indicated that most of the compounds demonstrated better in vitro antimycobacterial activity (MIC: 0.0383–7.53 μM) than diclofenac (MIC: 21.10 μM) and ciprofloxacin (MIC: 9.41 μM). Among the synthesized compounds, 1-cyclopropyl-6-fluoro-8-methoxy-7-[[N4-(2-(2-(2,6-dichlorophenylamino)phenyl)acetyl)-3-methyl]-N1-piperazinyl]-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (5d) was found to be the most active compound in vitro with MIC of 0.0383 μM and was more potent than first line antitubercular drug isoniazid (MIC: 0.1822 μM). In the in vivo animal model 5d decreased the bacterial load in lung and spleen tissues with 2.42 − and 3.66 − log 10 protections, respectively, at 25 mg/kg body weight.

Various diclofenac acid hydrazones and amides were synthesized and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis. Among the synthesized compounds, 1-cyclopropyl-6-fluoro-8-methoxy-7-[[N4-(2-(2-(2,6-dichlorophenylamino)phenyl)acetyl)-3-methyl]-N1-piperazinyl]-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (5d) was found to be the most active compound in vitro with MIC of 0.0383 μM and was more potent than the first line antitubercular drug isoniazid (MIC: 0.1822 μM).Figure optionsDownload as PowerPoint slide