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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MDPI AG
2024-10-01
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| Series: | Antibiotics |
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| author | Kerrin Hainsworth Melissa M. Cadelis Florent Rouvier Jean Michel Brunel Brent R. Copp |
| author_facet | Kerrin Hainsworth Melissa M. Cadelis Florent Rouvier Jean Michel Brunel Brent R. Copp |
| author_sort | Kerrin Hainsworth |
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| description | 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. |
| format | Article |
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| institution | OA Journals |
| issn | 2079-6382 |
| language | English |
| publishDate | 2024-10-01 |
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| series | Antibiotics |
| spelling | doaj-art-ec6ac71094104f4ea113dede3e50ace42025-08-20T02:08:00ZengMDPI AGAntibiotics2079-63822024-10-011311101810.3390/antibiotics13111018Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin DerivativesKerrin Hainsworth0Melissa M. Cadelis1Florent Rouvier2Jean Michel Brunel3Brent R. Copp4School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New ZealandSchool of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New ZealandMembranes et Cibles Thérapeutiques, SSA, INSERM, Aix-Marseille Universite, 27 bd Jean Moulin, 13385 Marseille, FranceMembranes et Cibles Thérapeutiques, SSA, INSERM, Aix-Marseille Universite, 27 bd Jean Moulin, 13385 Marseille, FranceSchool of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New ZealandIn 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.https://www.mdpi.com/2079-6382/13/11/1018pleuromutilinpotentiationadjuvantantimicrobialantibioticsantifungal agents |
| spellingShingle | Kerrin Hainsworth Melissa M. Cadelis Florent Rouvier Jean Michel Brunel Brent R. Copp Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives Antibiotics pleuromutilin potentiation adjuvant antimicrobial antibiotics antifungal agents |
| title | Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives |
| title_full | Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives |
| title_fullStr | Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives |
| title_full_unstemmed | Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives |
| title_short | Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives |
| title_sort | synthesis and antibacterial activity of alkylamine linked pleuromutilin derivatives |
| topic | pleuromutilin potentiation adjuvant antimicrobial antibiotics antifungal agents |
| url | https://www.mdpi.com/2079-6382/13/11/1018 |
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