Synthesis and Anti-Leishmanial Properties of Quinolones Derived from Zanthosimuline
Quinoline derivatives and especially quinolones are considered as privileged structures in medicinal chemistry and are often associated with various biological properties. We recently isolated a series of original monoterpenyl quinolones from the bark of <i>Codiaeum peltatum</i>. As this...
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| author | Gwenaëlle Jézéquel Laura Nogueira de Faria Cardoso Florent Olivon Indira Dennemont Cécile Apel Marc Litaudon Fanny Roussi Sébastien Pomel Sandy Desrat |
| author_facet | Gwenaëlle Jézéquel Laura Nogueira de Faria Cardoso Florent Olivon Indira Dennemont Cécile Apel Marc Litaudon Fanny Roussi Sébastien Pomel Sandy Desrat |
| author_sort | Gwenaëlle Jézéquel |
| collection | DOAJ |
| description | Quinoline derivatives and especially quinolones are considered as privileged structures in medicinal chemistry and are often associated with various biological properties. We recently isolated a series of original monoterpenyl quinolones from the bark of <i>Codiaeum peltatum</i>. As this extract was found to have a significant inhibitory activity against a <i>Leishmania</i> species, we decided to study the anti-leishmanial potential of this type of compound. Leishmaniasis is a serious health problem affecting more than 12 million people in the world. Available drugs cause harmful side effects and resistance for some of them. With the aim of finding anti-leishmanial compounds, we developed a synthetic strategy to access natural quinolones and analogues derived from zanthosimuline. We showed the versatility of this natural compound toward cyclization conditions, leading to various polycyclic quinolone-derived structures. The natural and synthetic compounds were evaluated against amastigote forms of <i>Leishmania infantum</i>. The results obtained confirmed the interest of this family of natural compounds but also revealed promising activities for some intermediates deriving from zanthosimuline. Following the same synthetic strategy, we then prepared 14 new analogues. In this work, we identified two promising molecules with good activities against intramacrophage <i>L. infantum</i> amastigotes without any cytotoxicity. We also showed that slight changes in amide functional groups affect drastically their anti-parasitic activity. |
| first_indexed | 2024-03-09T18:07:08Z |
| format | Article |
| id | doaj.art-9740a22337734f6582856a044efcb85f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:07:08Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9740a22337734f6582856a044efcb85f2023-11-24T09:22:54ZengMDPI AGMolecules1420-30492022-11-012722789210.3390/molecules27227892Synthesis and Anti-Leishmanial Properties of Quinolones Derived from ZanthosimulineGwenaëlle Jézéquel0Laura Nogueira de Faria Cardoso1Florent Olivon2Indira Dennemont3Cécile Apel4Marc Litaudon5Fanny Roussi6Sébastien Pomel7Sandy Desrat8CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, FranceCNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, FranceCNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, FranceCNRS, BioCIS, Université Paris-Saclay, 92290 Châtenay-Malabry, FranceCNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, FranceCNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, FranceCNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, FranceCNRS, BioCIS, Université Paris-Saclay, 92290 Châtenay-Malabry, FranceCNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, FranceQuinoline derivatives and especially quinolones are considered as privileged structures in medicinal chemistry and are often associated with various biological properties. We recently isolated a series of original monoterpenyl quinolones from the bark of <i>Codiaeum peltatum</i>. As this extract was found to have a significant inhibitory activity against a <i>Leishmania</i> species, we decided to study the anti-leishmanial potential of this type of compound. Leishmaniasis is a serious health problem affecting more than 12 million people in the world. Available drugs cause harmful side effects and resistance for some of them. With the aim of finding anti-leishmanial compounds, we developed a synthetic strategy to access natural quinolones and analogues derived from zanthosimuline. We showed the versatility of this natural compound toward cyclization conditions, leading to various polycyclic quinolone-derived structures. The natural and synthetic compounds were evaluated against amastigote forms of <i>Leishmania infantum</i>. The results obtained confirmed the interest of this family of natural compounds but also revealed promising activities for some intermediates deriving from zanthosimuline. Following the same synthetic strategy, we then prepared 14 new analogues. In this work, we identified two promising molecules with good activities against intramacrophage <i>L. infantum</i> amastigotes without any cytotoxicity. We also showed that slight changes in amide functional groups affect drastically their anti-parasitic activity.https://www.mdpi.com/1420-3049/27/22/7892quinolonenatural products<i>Leishmania</i> |
| spellingShingle | Gwenaëlle Jézéquel Laura Nogueira de Faria Cardoso Florent Olivon Indira Dennemont Cécile Apel Marc Litaudon Fanny Roussi Sébastien Pomel Sandy Desrat Synthesis and Anti-Leishmanial Properties of Quinolones Derived from Zanthosimuline Molecules quinolone natural products <i>Leishmania</i> |
| title | Synthesis and Anti-Leishmanial Properties of Quinolones Derived from Zanthosimuline |
| title_full | Synthesis and Anti-Leishmanial Properties of Quinolones Derived from Zanthosimuline |
| title_fullStr | Synthesis and Anti-Leishmanial Properties of Quinolones Derived from Zanthosimuline |
| title_full_unstemmed | Synthesis and Anti-Leishmanial Properties of Quinolones Derived from Zanthosimuline |
| title_short | Synthesis and Anti-Leishmanial Properties of Quinolones Derived from Zanthosimuline |
| title_sort | synthesis and anti leishmanial properties of quinolones derived from zanthosimuline |
| topic | quinolone natural products <i>Leishmania</i> |
| url | https://www.mdpi.com/1420-3049/27/22/7892 |
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