Synthesis and structure-activity relationship of novel thiazole aminoguanidines against MRSA and Escherichia coli

Novel lead thiazole aminoguanidines exhibited strong activity against Gram-positive bacteria. The potential targets of these substances are undecaprenyl diphosphate synthase (UPPS) and undecaprenyl diphosphate phosphatase (UPPP). Here, we report the synthesis and antibacterial evaluation of a library of thiazole aminoguanidines analogues, wherein the rotatable bond is inserted between the C2 position of thiazole and hydrophobic group. The molecular flexibility is increased, and new analogues with strong activity against MRSA and E. coli are produced. The best compound 4i showed rapid sterilization and low tendency to induce bacterial resistance. The IC50 of compound 4i to EcUPPS enzyme is 145 mu mol L-1 (58 mu g mL(-1)). Compound 4i can also inhibit and destroy bacterial biofilms. These thiazole aminoguanidines can be developed as potential therapeutic candidates in the future.