Investigation of Ugi-4CC derived 1H-tetrazol-5-yl-(aryl) methyl piperazinyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid: synthesis, biology and 3D-QSAR analysis.
Novel series of 7-piperazinylquinolones with tetrazole derivatives were synthesized and evaluated for their antibacterial activity against various strains of Staphylococcus aureus. All the synthesized compounds showed significant in vitro antibacterial activity against Gram-positive bacteria whereas some compounds displayed moderate activity against Gram-negative bacteria. Among all the synthesized compounds, compounds (6a-c, 6e-g, 6i-k, 6m, 6'f and 6'm) were found to be more effective with MIC ranging from (0.78-3.12 μg/mL) against S. aureus (ATCC-29213) than the control; ciprofloxacin (MIC = 25 μg/mL). Moreover, these analogues displayed no toxicity up to MIC = 0.39 μg/mL against mammalian cell line L-929. Furthermore, to correlate the biological activities of synthesized compounds with their 3D conformation, we attempted 3D-QSAR study.
Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
Kuldeep
K
Chauhan
Microbiology Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
Pratiksha
P
Singh
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
Vikash
V
Kumar
Microbiology Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
Praveen K
PK
Shukla
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
Mohammad Imran
MI
Siddiqi
Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India. Electronic address: prem_chauhan_2000@yahoo.com.
Prem M S
PM
Chauhan
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology*
C000593741:7-piperazinylquinolone; D000900:Anti-Bacterial Agents; D010879:Piperazines; D015363:Quinolones; D013777:Tetrazoles; C045574:1H-tetrazole
3D-QSAR analysis; Antibacterial activity; Cytotoxicity; Fluoroquinolones; Tetrazole