Synthesis and in vitro activity of asymmetric indole-based bisamidine compounds against Gram-positive and Gram-negative pathogens.
Chen X, Liu Y, Wang C, Hu X, Wu Y, Zhang Y, Bian C, You X, Hu L.
A series of new asymmetric bisamidine was designed, synthesized, and tested for their in-vitro antibacterial activity using a range of Gram-positive and Gram-negative pathogens. Most compounds demonstrated powerful antibacterial activity, and interestingly, some displayed better activity against several Gram-negative strains than the lead compound 1. The most potent bisamidine 8l exhibited 4-fold more potent activity against E. coli, K. pneumonia, P. aeruginosa, and C. freundii than compound 1. Especially 8l exhibited a powerful activity against K. pneumonia secreting NDM-1 enzyme with a minimum inhibitory concentration (MIC) of 2 μg/mL, while levofloxacin and vancomycin displayed resistance, with MICs > 128 μg/mL.