ABSTRACT
A series of seventeen new 6-(4-substitutedpiperazin-1-yl)phenanthridine derivatives were designed, synthesized, and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv by Microplate Alamar Blue Assay and most active compounds were tested for cytotoxicity studies against mouse macrophage cell lines (RAW264.7). Among the tested compounds, ten compounds exhibited significant activity against the growth of M. tuberculosis (MIC ranging from 1.56 to 6.25 µg/mL). In particular, compounds 5e, 5j and 5k displayed excellent activity against the growth of M. tuberculosis (MIC 1.56 µg/mL). The selectivity index values were found to be >25, indicating compounds likeliness in drug development for tuberculosis. The structure of 5k is substantiated by X-ray crystallographic study. Structure-activity correlation indicates the importance of substituent at 4th position of piperazinyl phenanthridine ring.
Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Phenanthridines/chemical synthesis , Phenanthridines/pharmacology , Animals , Cell Line , Crystallography, X-Ray , Macrophages/drug effects , Magnetic Resonance Spectroscopy , Mice , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Spectrometry, Mass, Electrospray IonizationABSTRACT
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 ((1)H NMR, (13)C 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.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Carboxylic Acids/chemistry , Carboxylic Acids/pharmacology , Quinolines/chemistry , Quinolines/pharmacology , Escherichia coli/drug effects , Escherichia coli Infections/drug therapy , Halogenation , Humans , Mycobacterium tuberculosis/drug effects , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Structure-Activity Relationship , Tuberculosis/drug therapyABSTRACT
A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substituted piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized ((1)H NMR, (13)C NMR and LCMS) and evaluated for their inhibitory activity on the proliferation of human caucasian acute lymphoblastic leukemia cells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin analogues 3t at 50 µM showed comparable potency to doxorubicin (10 µM) in all three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35% selectively over other two cell lines.
