Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives
In an effort to expand the spectrum of the antibacterial activity of pleuromutilin, a series of amine- and polyamine-linked analogues were prepared and evaluated for activities against a panel of microorganisms. Simple C-22-substituted amino esters or diamines <b>16</b>, <b>17</...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/13/11/1018 |
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| Summary: | In an effort to expand the spectrum of the antibacterial activity of pleuromutilin, a series of amine- and polyamine-linked analogues were prepared and evaluated for activities against a panel of microorganisms. Simple C-22-substituted amino esters or diamines <b>16</b>, <b>17</b>, <b>18</b>, and <b>22</b>, as well as two unusual amine-linked bis-pleuromutilin examples <b>20</b> and <b>23</b>, displayed variable levels of activity towards <i>Staphylococcus aureus</i> ATCC 25923 and methicillin-resistant <i>S. aureus</i>, but with no detectable activities towards Gram-negative bacteria. Fortunately, the incorporation of a longer-chain triamine or polyamine (spermine) at C-22 did afford analogues (<b>30</b>, <b>31</b>) that exhibited activity towards both <i>S. aureus</i> ATCC 25923 and <i>Escherichia coli</i> ATCC 25922 with MIC 6.1–13.4 µM. Spermine–pleuromutilin analogue <b>31</b> was also able to enhance the action of doxycycline towards <i>Pseudomonas aeruginosa</i> ATCC 27853 by eight-fold, highlighting it as a useful scaffold for the development of new antibacterial pleuromutilin analogues that exhibit a broader spectrum of activity. |
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| ISSN: | 2079-6382 |