Diethyl (5-Benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate
As part of our ongoing research into the antileishmanial properties of amidoxime derivatives, we report a preliminary assessment of the antiparasitic properties of a novel compound, diethyl (5-benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate....
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Molbank |
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| Online Access: | https://www.mdpi.com/1422-8599/2023/4/M1736 |
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| author | Oscar Leonardo Avendaño Leon Christophe Curti Fabiana Maia Santos Urbancg Moncorvo Youssef Kabri Sébastien Redon Eduardo Caio Torres-Santos Romain Paoli-Lombardo Patrice Vanelle |
| author_facet | Oscar Leonardo Avendaño Leon Christophe Curti Fabiana Maia Santos Urbancg Moncorvo Youssef Kabri Sébastien Redon Eduardo Caio Torres-Santos Romain Paoli-Lombardo Patrice Vanelle |
| author_sort | Oscar Leonardo Avendaño Leon |
| collection | DOAJ |
| description | As part of our ongoing research into the antileishmanial properties of amidoxime derivatives, we report a preliminary assessment of the antiparasitic properties of a novel compound, diethyl (5-benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate. This compound was evaluated in vitro for the first time against the promastigote form of <i>Leishmania amazonensis</i>. Compounds containing both amidoxime and phosphonyl functional groups in dihydrofuran scaffolds are relatively rare, despite the extensive study of this heterocycle in various biological applications. Therefore, this work makes a valuable contribution to the fight against <i>Leishmania</i> spp. as a neglected disease. The cyclized 4,5-dihydrofuran intermediate scaffold was obtained via a three-step synthetic route that had previously been developed for accessing other derivatives, including the sulfone moiety. This synthesis was performed using a manganese-based free radical oxidative method under microwave irradiation. The intermediary 4,5-dihydrofuran, which included a nitrile group, tolerated the subsequent reaction with hydroxylamine hydrochloride, resulting in the formation of the target product. The target compound showed moderate activity in vitro against the promastigote form of <i>L. amazonensis</i> (IC<sub>50</sub> = 91.1 µM). |
| first_indexed | 2024-03-08T20:31:23Z |
| format | Article |
| id | doaj.art-e55fadfa457e490a80ac0f4274d10c39 |
| institution | Directory Open Access Journal |
| issn | 1422-8599 |
| language | English |
| last_indexed | 2024-03-08T20:31:23Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molbank |
| spelling | doaj.art-e55fadfa457e490a80ac0f4274d10c392023-12-22T14:27:02ZengMDPI AGMolbank1422-85992023-10-0120234M173610.3390/M1736Diethyl (5-Benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonateOscar Leonardo Avendaño Leon0Christophe Curti1Fabiana Maia Santos Urbancg Moncorvo2Youssef Kabri3Sébastien Redon4Eduardo Caio Torres-Santos5Romain Paoli-Lombardo6Patrice Vanelle7Aix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, CEDEX 05, 13385 Marseille, FranceAix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, CEDEX 05, 13385 Marseille, FranceLaboratório de Bioquímica de Tripanossomatídeos, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365, Rio de Janeiro 21040-900, BrazilAix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, CEDEX 05, 13385 Marseille, FranceAix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, CEDEX 05, 13385 Marseille, FranceLaboratório de Bioquímica de Tripanossomatídeos, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365, Rio de Janeiro 21040-900, BrazilAix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, CEDEX 05, 13385 Marseille, FranceAix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, CEDEX 05, 13385 Marseille, FranceAs part of our ongoing research into the antileishmanial properties of amidoxime derivatives, we report a preliminary assessment of the antiparasitic properties of a novel compound, diethyl (5-benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate. This compound was evaluated in vitro for the first time against the promastigote form of <i>Leishmania amazonensis</i>. Compounds containing both amidoxime and phosphonyl functional groups in dihydrofuran scaffolds are relatively rare, despite the extensive study of this heterocycle in various biological applications. Therefore, this work makes a valuable contribution to the fight against <i>Leishmania</i> spp. as a neglected disease. The cyclized 4,5-dihydrofuran intermediate scaffold was obtained via a three-step synthetic route that had previously been developed for accessing other derivatives, including the sulfone moiety. This synthesis was performed using a manganese-based free radical oxidative method under microwave irradiation. The intermediary 4,5-dihydrofuran, which included a nitrile group, tolerated the subsequent reaction with hydroxylamine hydrochloride, resulting in the formation of the target product. The target compound showed moderate activity in vitro against the promastigote form of <i>L. amazonensis</i> (IC<sub>50</sub> = 91.1 µM).https://www.mdpi.com/1422-8599/2023/4/M1736amidoxime4,5-dihydrofuran-phosphonyl derivativeleishmaniasismicrowave irradiation |
| spellingShingle | Oscar Leonardo Avendaño Leon Christophe Curti Fabiana Maia Santos Urbancg Moncorvo Youssef Kabri Sébastien Redon Eduardo Caio Torres-Santos Romain Paoli-Lombardo Patrice Vanelle Diethyl (5-Benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate Molbank amidoxime 4,5-dihydrofuran-phosphonyl derivative leishmaniasis microwave irradiation |
| title | Diethyl (5-Benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate |
| title_full | Diethyl (5-Benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate |
| title_fullStr | Diethyl (5-Benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate |
| title_full_unstemmed | Diethyl (5-Benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate |
| title_short | Diethyl (5-Benzyl-2-(4-(<i>N</i>′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate |
| title_sort | diethyl 5 benzyl 2 4 i n i hydroxycarbamimidoyl phenyl 5 methyl 4 5 dihydrofuran 3 yl phosphonate |
| topic | amidoxime 4,5-dihydrofuran-phosphonyl derivative leishmaniasis microwave irradiation |
| url | https://www.mdpi.com/1422-8599/2023/4/M1736 |
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