With antibiotics resistance developing rapidly, new antibacterial agents are needed to be discovered. We readily synthesized 11 indolin-2-one compounds and found a hybrid of indolin-2-one and nitroimidazole 3-((1-methyl-5-nitro-1H-imidazol-2-yl)methylene)indolin-2-one to be effective on Staphylococcus aureus strains. Six derivatives of this compound were further designed and synthesized in order to enhance its efficacy. After a second turn of structural refinement, a novel hybrid of indolin-2-one and nitroimidazole 3-((1-methyl-5-nitro-1H-imidazol-2-yl)methylene)-5-nitroindolin-2-one with a nitro group on C-5 position of indolin-2-one was shown to exhibit remarkable antibacterial activities with a low MIC value against MRSA ATCC 33591. Besides, this molecule demonstrated its potency on Gram-negative bacteria and VRE strain. The time-killing curve experiment showed its good bactericidal activity. Low hemolytic rate suggested its promising safety profile.
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This work was financially supported by grants from the National Natural Science Foundation of China (Grant NO. 81602956 and 81473253), National Major Program of China during the 13th Five-Year Plan Period (Grant NO. 2018ZX09721001-001-001), and China Postdoctoral Science Foundation (Grant NO. 2016M590895). Thank Sichuan Provincial People’s Hospital for the supply of VRE B148 strains.
Conflict of interest
The authors declare that they have no conflict of interest.
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