Synthesis and antibacterial activities of baulamycin A inspired derivatives

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SbnE is an essential enzyme for staphyloferrin B biosynthesis in Staphylococcus aureus . An earlier study showed that natural product baulamycin A has in vitro inhibitory activity against SbnE and antibacterial potency. A SAR study with analogues of baulamycin A was conducted to identify potent inhibitors of SbnE and/or effective antibiotics against MRSA . The results show that selected analogues, including 11 , 18 , 21 , 24a , 24c , 24m and 24n , exhibit single-digit micromolar inhibitory potencies against SbnE (IC 50 s = 1.81–8.94 μM) and 11 , 24m , 24n possess significant activities against both SbnE (IC 50 s = 4.12–6.12 μM) and bacteria (MICs = 4–32 μg/mL). Biological investigations revealed that these substances possess potent cell wall disruptive activities and that they inhibit siderophore production in MRSA . Among the selected analogues, 7 has excellent antibiotic activities both gram-positive and –negative bacteria (0.5–4 μg/mL). Moreover, these analogues significantly impede biofilm formation in a concentration-dependent manner. Taken together, the results of the investigation provide valuable insight into the nature of novel baulamycin A analogues that have potential efficacy against MRSA owing to their membrane damaging activity and/or inhibitory efficacy against siderophore production.