Design, synthesis and biological evaluation of novel ocotillol-type triterpenoid derivatives as antibacterial agents

A new series of hydrophilic ocotillol-type triterpenoid derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Gram-positive and Gram-negative bacteria. Among which, compounds 9, 10, 11c, 12c, 13a-d and 14a-d displayed potent antibacterial activity against Gram-positive bacteria with MIC values of 1-16 mu g/mL. Furthermore, additional testing against MRSA USA300 demonstrated that compounds 9, 13b, 13c and 14c also possess good antibacterial activity with MIC values of 2-8 mu g/mL. The bactericidal effects revealed that compounds 9, 13b and 13c displayed directly bactericidal activity against B. subtilis and MRSA USA300 with MBC values of 2-16 mu g/mL. The subsequent synergistic activity assay showed that compounds 13b and 13c could enhance the susceptibility of MRSA USA300 and B. subtilis to kanamycin and chloramphenicol (FICI < 0.5). Compounds 13b and 13c were then evaluated for their cytotoxicity and displayed low toxicity at their antibacterial MICs. The optimized structure-activity relationship was also concluded.