New MraY<sub>AA</sub> Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole
New inhibitors of the bacterial transferase MraY from <i>Aquifex aeolicus</i> (MraY<sub>AA</sub>), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Book |
| Published: |
MDPI AG,
2022-09-01T00:00:00Z.
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| Subjects: | |
| Online Access: | Connect to this object online. |
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| Summary: | New inhibitors of the bacterial transferase MraY from <i>Aquifex aeolicus</i> (MraY<sub>AA</sub>), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin. A panel of ten compounds was synthetized notably thanks to a robust microwave-activated one-step sequence for the synthesis of the oxadiazole ring that involved the <i>O</i>-acylation of an amidoxime and subsequent cyclization. The synthetized compounds, with various hydrophobic substituents on the oxadiazole ring, were tested against the MraY<sub>AA</sub> transferase activity. Although with poor antibacterial activity, nine out of the ten compounds revealed the inhibition of the MraY<sub>AA</sub> activity in the range of 0.8 µM to 27.5 µM. |
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| Item Description: | 10.3390/antibiotics11091189 2079-6382 |