Synthesis And Evaluation Of The Antibacterial Activities Of Rhodanine Derivatives Containing L-Tryptophan

In resent years, many new antibacterial drugs are put into production, but the bacterial infectious disease have seriously threatened to people’s life and health. There are many reasons for this phenomenon, but the most important reason is that the improper use of antibiotics for human beings, bacterium emerge the resistance to drugs, then antibacterial agents reduce the effect of antibacterial. In order to overcome the threat of antibacterial infection and ensure the safety of human life, for human beings the most important task is to discover new moieties with antibacterial activity and develop them to drug through modifying and optimizing the structures.In order to discover compounds which have better antibacterial activity, we searched a lot of paper and found rhodanine derivatives with antibacterial activity. In previous years, we synthesized a large number of rhodanine derivatives, and found that rhodanine derivatives bearing tryptophan structure showed better antibacterial activity than ones bearing other amino acid. Based on this information, we used the compound B containing tryptophan structure as a lead compound, and then designed and synthesized four series of compounds such as 4a-e, 7a-d, 10a-e,13a-d. All of synthesized compounds showed potent inhibition of four Gram-positive strains (S. aurerus 4220, S. aureus 209, S. aureus 503, S. mutans 3289), four Gram-negative strains (E. coli 1924, S. aeruginosa 2742, S. aeruginosa 2004, S. typhinurium 2421) and one fungus with minimum inhibitory concentraton (MIC) values in the range of 1-64 μg/mL. In gram-positive bacteria test,7c, 10e,13a showed the best activity with same MIC value of 2 μg/mL, it was same or similar antibacterial activity compares to the positive control drug moxifloxacin and gatifloxacin. Four series of compounds showed good antibacterial activity against four clinical MDR Gram-positivve strains with MIC values in the range of 2-16 ug/mL Among them,4c, 10e,13c show the best activity with same MIC value of 2 μg/mL. The 4c, 10e and 13c (MIC=2 μg/mL) showed similar activity with the positive control drug moxifloxacin (MIC=1 μg/mL) and gatifloxacin(MIC=2μg/mL)against MRSA.Moreover,they(MIC =2μg/mL)showed 2- and 4-fold higher activity than the positive control drug moxifloxacin(MIC=4 μg/mL)and gatifloxacin(MIC= 4-8 μg/mL)against QRSA.