Synthesis and evaluation of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-(2-(4-substitutedpiperazin-1-yl)acetyl)piperazin-1-yl)quinoline-3-carboxylic acid derivatives as anti-tubercular and antibacterial agents

• Published in: European journal of medicinal chemistry Vol. 71; pp. 324 - 332
• Main Authors: Suresh, Narva, Nagesh, Hunsur Nagendra, Renuka, Janupally, Rajput, Vikrant, Sharma, Rashmi, Khan, Inshad Ali, Kondapalli Venkata Gowri, Chandra Sekhar
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2014
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-tubercular activity; Antibacterial activity; Carboxylic Acids - chemistry; Carboxylic Acids - pharmacology; Cytotoxicity; Escherichia coli - drug effects; Escherichia coli Infections - drug therapy; Fluoroquinolone; Halogenation; Humans; Mycobacterium tuberculosis - drug effects; Quinolines - chemistry; Quinolines - pharmacology; Staphylococcal Infections - drug therapy; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Supercoiling assay; Tuberculosis - drug therapy; Antibacterial activity; Cytotoxicity; Anti-tubercular activity; Fluoroquinolone; Supercoiling assay
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.10.055

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues were synthesized, characterized (1H NMR, 13C NMR and LCMS) and screened for their in vitro anti-tubercular and antibacterial activity. Many of these compounds exhibited MIC values in the range 7.32–136.10 μM against Mycobacterium tuberculosis H37Rv. Eight compounds were further subjected to cytotoxic studies. Furthermore, the title compounds were screened for antibacterial activity against Staphylococcus aureus ATCC 29213 (gram positive) and Escherichia coli ATCC 25922 (gram negative) bacteria. Many of these compounds exhibited MIC values in the range 0.44–34.02 μM. Compound 3f was found to be the most active with an MIC of 0.44 and 0.8 μM respectively against both the strains. In general, the antibacterial activity of title compounds was more prominent. [Display omitted] •22 ciprofloxacin derivatives were evaluated for antitubercular and antibacterial activity.•Compound 3d emerged as most active against MTB H37Rv strain (MIC 7.32 µM).•Further compound 3d exhibited IC50 = 7 µM against DNA gyrase supercoiling assay.•Compound 3f is most active against ATCC29213 (MIC 0.44 µM) and ATCC 25922 (MIC 0.88 µM).•Antibacterial activity of title compounds was promising than antitubercular activity.