Synthesis and Antibacterial Activities of Novel Sulphonamide Containing 1, 3-diarylpyrazolyl Amides (2018)

Background: Infectious diseases are the leaders among the challenging drug targets because of the multi-drug resist antimicrobial pathogens and continuous rise in the emerging infections from known and unknown sources. Though there is an availability of a large number of antibiotics and chemotherapeutics for medical use, the emerging resistance drives it for the search of new classes of antimicrobial agents. In the present study, a series of novel amides (5a-j) containing 1, 3-diaryl pyrazoles were synthesized, characterized and evaluated for their anti-bacterial properties against gram - positive organisms (B. subtilis) and gram - negative organisms (E. coli). Method: The evaluation of the synthesized compounds (5a-j) for antibacterial activity was carried out by standard literature procedure using agar diffusion method by finding the zone of inhibition of the drug sample against the standard drugs. The organisms employed in vitro testing of the compounds were Escherichia coli (Gram Negative) and Bacillus subtilis (Gram Positive). All the cultures were maintained on Nutrient agar (Microbiology) grade, Hi Media medium by periodic sub culturing. Ciprofloxacin was used as reference compound for antibacterial activity. The compounds were tested at a concentration of a 50 µg/ml and 100 µg/ml and were prepared in Dimethylsulphoxide. Obtained zone of inhibition at tested concentrations was recorded. Minimum inhibitory concentrations (MIC) assay of two superior molecules 5e and 5f was done according to CLSI standard protocol. Ciprofloxacin was used as a standard drug. The minimum inhibitory concentrations (MIC) values were determined. Results: The structures of these novel compounds were confirmed by 1H NMR, ES-MS and elemental analysis. Ciprofloxacin was used as standard reference compound. In the initial inhibitory study at 100 µg/ml, compounds 5e (12 ± 0.816) and 5f (17 ± 0.816) demonstrated comparable zone of inhibition with ciprofloxacin (20.66 ± 0.942) in E. coli strain, while for B. subtilis, at 100µg/ml, compounds 5e (25.66 ± 0.942) and 5f (26.33 ± 0.942) were found to be equipotent as compared to standard ciprofloxacin (27.66 ± 0.471). Hence 5e and 5f were tested for their MIC values (µg/ml) using E. coli and B. subtilis bacterial strains. To summarize, 5e (MIC = 8µg/ml for E. coli and MIC = 4 µg/ml for B. subtilis) and 5f (MIC = 16 µg/ml for E. coli and MIC = 8 µg/ml for B. subtilis) showed better MIC values than the standard Ciprofloxacin (MIC = 20 µg/ml for E. coli and MIC = 12 µg/ml for B. subtilis). Conclusion: We have discovered a series of 1, 3 diaryl pyrazolyl amides, and preliminary bioassay results imply that some of the compounds displayed moderate antibacterial activities against various bacterial species. Two promising compounds 5e and 5f exhibited superior MIC (µg/ml) values in vitro when compared with standard drug. Compounds 5e and 5f were the new findings from this research work and it will be studied further in near future. Keywords: 1, 3-diaryl pyrazole, 4-Hydrazino-benzenesulfonamide, sulfonamide, MIC, anti-bacterial activities.