Synthesis And Biological Evaluation Of 1,3-diaryl Pyrazole Derivatives As Potential Antibacterial And Anti-inflammatory Agents

The treatment of disease which is caused by bacterial infections is an urgent and challenging therapeutical puzzle with the continued occurence of multi-drug-resistant bacteria. Nowadays microorganism infection is a major concern and account for almost 50000 deaths worldwide daily. Drug-resistance bacteria kill more than two million people each year and endanger human health seriously. Owing to the increasingly serious problems caused by Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates), there is an ongoing demand for new antibacterial agents.In this article, three series of 1,3-diary1 pyrazole derivatives bearing aminoguanidine or furan-2-carbohydrazide moieties have been synthesized, characterized and evaluated for their antimicrobial and anti-inflammatory activities. Most of the synthesized compounds showed potent inhibition of four Gram-positive strains (S. aureus RN 4220, S. aureus KTCT 209, S. aureus KTCT 503, Streptococcus mutans 3065), five Gram-negative strains (Pseudomonas aeruginosa 2742 and 2004, Escherichia coli KTCT 1924, Escherichia coli CCARM 1356, Salmonella typhimurium 2421) and one fungus (Candida albicans 7535) with minimum inhibitory concentration (MIC) values in the range of 1-64 jig/mL. Compounds 6g,61 and 71 presented the most potent inhibitory activity against Gram-positive bacteria (e.g. Staphylococcus aureus 4220), Gram-negative bacteria (e.g. Escherichia coli 1924) and the fungus, Candida albicans 7535, with minimum inhibitory concentration values of 1 or 2 p.g/mL. What’s more, compounds 61 and 71 displayed high levels of antibacterial activity against S. aureus RN 4220, S. aureus KTCT 209, S. aureus KTCT 503, MRSA CCARM 3506, QRSA CCARM (3505 and 3519) and E. coli KTCT 1924 with MBC values of 1 or 2 μg/mL. Compared with previous studies, these compounds exhibited a broad spectrum of inhibitory activity. Furthermore, compound 71 showed the greatest anti-inflammatory activity (93.59% inhibition,30 min after intraperitoneal administration), which was more potent than the reference drugs ibuprofen and indomethacin.