Selective Anti-Leishmanial Strathclyde Minor Groove Binders Using an N-Oxide Tail-Group Modification
The neglected tropical disease leishmaniasis, caused by Leishmania spp., is becoming more problematic due to the emergence of drug-resistant strains. Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an emerging class of anti-infective agent that have been shown to have potent activity against various bacteria, viruses, fungi and parasites. Herein, it is shown that S-MGBs have potent activity against L. donovani, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
International journal of molecular sciences - 23(2022), 19 vom: 07. Okt. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Perieteanu, Marina C [VerfasserIn] |
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| Links: |
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| Themen: |
9007-49-2 |
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| Anmerkungen: |
Date Completed 17.10.2022 Date Revised 01.03.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms231911912 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM347482783 |
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| 520 | |a The neglected tropical disease leishmaniasis, caused by Leishmania spp., is becoming more problematic due to the emergence of drug-resistant strains. Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an emerging class of anti-infective agent that have been shown to have potent activity against various bacteria, viruses, fungi and parasites. Herein, it is shown that S-MGBs have potent activity against L. donovani, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics | ||
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| 700 | 1 | |a Shaw, Craig D |e verfasserin |4 aut | |
| 700 | 1 | |a MacMillan, Donna S |e verfasserin |4 aut | |
| 700 | 1 | |a Khalaf, Abedawn I |e verfasserin |4 aut | |
| 700 | 1 | |a Gillingwater, Kirsten |e verfasserin |4 aut | |
| 700 | 1 | |a Beveridge, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Carter, Katharine C |e verfasserin |4 aut | |
| 700 | 1 | |a Suckling, Colin J |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Fraser J |e verfasserin |4 aut | |
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