Diastereomeric <i>N</i>,<i>S</i>-Dialkyl Dithiocarbamates Derived from (<i>E</i>)-Chalcones and ʟ-Tryptophan: Microwave-Assisted Synthesis and In Vitro Studies Against <i>Fusarium oxysporum</i>

The synthesis of indole phytoalexin-like analogs related to alkyl (((1-(4-substitutedphenyl)-3-oxo-3-phenylpropyl)thio)carbonothioyl)-ʟ-tryptophanate <b>1a</b>–<b>d</b> and the evaluation of their antifungal activity against the phytopathogen <i>Fusarium oxysporum</i...

Full description

Saved in:
Bibliographic Details
Main Authors: Natalia Agudelo-Ibañez, Sergio Torres-Cortés, Ericsson Coy-Barrera, Ivon Buitrago, Diego Quiroga
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Organics
Subjects:
Online Access:https://www.mdpi.com/2673-401X/5/4/31
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846103325516234752
author Natalia Agudelo-Ibañez
Sergio Torres-Cortés
Ericsson Coy-Barrera
Ivon Buitrago
Diego Quiroga
author_facet Natalia Agudelo-Ibañez
Sergio Torres-Cortés
Ericsson Coy-Barrera
Ivon Buitrago
Diego Quiroga
author_sort Natalia Agudelo-Ibañez
collection DOAJ
description The synthesis of indole phytoalexin-like analogs related to alkyl (((1-(4-substitutedphenyl)-3-oxo-3-phenylpropyl)thio)carbonothioyl)-ʟ-tryptophanate <b>1a</b>–<b>d</b> and the evaluation of their antifungal activity against the phytopathogen <i>Fusarium oxysporum</i> is reported. The target compounds were synthesized in the following two stages: (1) the initial esterification of ʟ-tryptophan, which reacted with trimethyl silane chloride and simple aliphatic alcohols (R = Me, Et) under microwave irradiation (MWI) at 100 °C to obtain the respective alkyl ester <b>2a</b>–<b>b</b>; (2) the resulting mixture of ʟ-tryptophanates <b>2a</b>–<b>b</b> with carbon disulfide and (<i>E</i>)-chalcone <b>3a</b>–<b>b</b> under MWI at 50 °C during 60 min, followed by purification through classical column chromatography (55–76% yields). The products were obtained as mixtures of (<i>S</i>,<i>R)</i> and (S,<i>S</i>) diastereoisomers. An LC-DAD-MS analysis allowed us to establish the ratio of these diastereoisomers, and subsequent DFT/B3LYP-based computational calculations of the NMR <sup>1</sup>H chemical shifts suggested that the major diastereoisomer involved an (<i>S</i>,<i>R</i>) absolute configuration, comprising more than 60% of the mixture. The compounds <b>1a</b>–<b>d</b> were subjected to an antifungal activity test against the phytopathogen <i>F. oxysporum</i> using an amended medium-based assay. Compound series <b>1</b> showed inhibition percentages of 80% at the first concentration and IC<sub>50</sub> values between 0.33 and 5.71 mM, demonstrating greater potential as antifungal agents compared to other ʟ-tryptophan derivatives like alkyl (2<i>S</i>)-3-(1<i>H</i>-indol-3-yl)-2-{[(1<i>Z</i>)-3-oxobut-1-en-1-yl]amino}propanoate, which presented lower inhibition percentages. In summary, phytoalexin analogs derived from ʟ-tryptophan and (<i>E</i>)-chalcones significantly inhibited the mycelial growth of <i>Fusarium oxysporum</i>, indicating their potential as effective antifungal agents.
format Article
id doaj-art-ef3cd24ce00c44d0baa33d87230ed58e
institution Kabale University
issn 2673-401X
language English
publishDate 2024-12-01
publisher MDPI AG
record_format Article
series Organics
spelling doaj-art-ef3cd24ce00c44d0baa33d87230ed58e2024-12-27T14:44:58ZengMDPI AGOrganics2673-401X2024-12-015459861310.3390/org5040031Diastereomeric <i>N</i>,<i>S</i>-Dialkyl Dithiocarbamates Derived from (<i>E</i>)-Chalcones and ʟ-Tryptophan: Microwave-Assisted Synthesis and In Vitro Studies Against <i>Fusarium oxysporum</i>Natalia Agudelo-Ibañez0Sergio Torres-Cortés1Ericsson Coy-Barrera2Ivon Buitrago3Diego Quiroga4Bioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Cajicá 250247, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Cajicá 250247, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Cajicá 250247, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Cajicá 250247, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Cajicá 250247, ColombiaThe synthesis of indole phytoalexin-like analogs related to alkyl (((1-(4-substitutedphenyl)-3-oxo-3-phenylpropyl)thio)carbonothioyl)-ʟ-tryptophanate <b>1a</b>–<b>d</b> and the evaluation of their antifungal activity against the phytopathogen <i>Fusarium oxysporum</i> is reported. The target compounds were synthesized in the following two stages: (1) the initial esterification of ʟ-tryptophan, which reacted with trimethyl silane chloride and simple aliphatic alcohols (R = Me, Et) under microwave irradiation (MWI) at 100 °C to obtain the respective alkyl ester <b>2a</b>–<b>b</b>; (2) the resulting mixture of ʟ-tryptophanates <b>2a</b>–<b>b</b> with carbon disulfide and (<i>E</i>)-chalcone <b>3a</b>–<b>b</b> under MWI at 50 °C during 60 min, followed by purification through classical column chromatography (55–76% yields). The products were obtained as mixtures of (<i>S</i>,<i>R)</i> and (S,<i>S</i>) diastereoisomers. An LC-DAD-MS analysis allowed us to establish the ratio of these diastereoisomers, and subsequent DFT/B3LYP-based computational calculations of the NMR <sup>1</sup>H chemical shifts suggested that the major diastereoisomer involved an (<i>S</i>,<i>R</i>) absolute configuration, comprising more than 60% of the mixture. The compounds <b>1a</b>–<b>d</b> were subjected to an antifungal activity test against the phytopathogen <i>F. oxysporum</i> using an amended medium-based assay. Compound series <b>1</b> showed inhibition percentages of 80% at the first concentration and IC<sub>50</sub> values between 0.33 and 5.71 mM, demonstrating greater potential as antifungal agents compared to other ʟ-tryptophan derivatives like alkyl (2<i>S</i>)-3-(1<i>H</i>-indol-3-yl)-2-{[(1<i>Z</i>)-3-oxobut-1-en-1-yl]amino}propanoate, which presented lower inhibition percentages. In summary, phytoalexin analogs derived from ʟ-tryptophan and (<i>E</i>)-chalcones significantly inhibited the mycelial growth of <i>Fusarium oxysporum</i>, indicating their potential as effective antifungal agents.https://www.mdpi.com/2673-401X/5/4/31ʟ-tryptophan derivativeschalcone derivativesindolic phytoalexinmicrowave-assisted synthesis<i>Fusarium oxysporum</i>
spellingShingle Natalia Agudelo-Ibañez
Sergio Torres-Cortés
Ericsson Coy-Barrera
Ivon Buitrago
Diego Quiroga
Diastereomeric <i>N</i>,<i>S</i>-Dialkyl Dithiocarbamates Derived from (<i>E</i>)-Chalcones and ʟ-Tryptophan: Microwave-Assisted Synthesis and In Vitro Studies Against <i>Fusarium oxysporum</i>
Organics
ʟ-tryptophan derivatives
chalcone derivatives
indolic phytoalexin
microwave-assisted synthesis
<i>Fusarium oxysporum</i>
title Diastereomeric <i>N</i>,<i>S</i>-Dialkyl Dithiocarbamates Derived from (<i>E</i>)-Chalcones and ʟ-Tryptophan: Microwave-Assisted Synthesis and In Vitro Studies Against <i>Fusarium oxysporum</i>
title_full Diastereomeric <i>N</i>,<i>S</i>-Dialkyl Dithiocarbamates Derived from (<i>E</i>)-Chalcones and ʟ-Tryptophan: Microwave-Assisted Synthesis and In Vitro Studies Against <i>Fusarium oxysporum</i>
title_fullStr Diastereomeric <i>N</i>,<i>S</i>-Dialkyl Dithiocarbamates Derived from (<i>E</i>)-Chalcones and ʟ-Tryptophan: Microwave-Assisted Synthesis and In Vitro Studies Against <i>Fusarium oxysporum</i>
title_full_unstemmed Diastereomeric <i>N</i>,<i>S</i>-Dialkyl Dithiocarbamates Derived from (<i>E</i>)-Chalcones and ʟ-Tryptophan: Microwave-Assisted Synthesis and In Vitro Studies Against <i>Fusarium oxysporum</i>
title_short Diastereomeric <i>N</i>,<i>S</i>-Dialkyl Dithiocarbamates Derived from (<i>E</i>)-Chalcones and ʟ-Tryptophan: Microwave-Assisted Synthesis and In Vitro Studies Against <i>Fusarium oxysporum</i>
title_sort diastereomeric i n i i s i dialkyl dithiocarbamates derived from i e i chalcones and l tryptophan microwave assisted synthesis and in vitro studies against i fusarium oxysporum i
topic ʟ-tryptophan derivatives
chalcone derivatives
indolic phytoalexin
microwave-assisted synthesis
<i>Fusarium oxysporum</i>
url https://www.mdpi.com/2673-401X/5/4/31
work_keys_str_mv AT nataliaagudeloibanez diastereomericiniisidialkyldithiocarbamatesderivedfromieichalconesandʟtryptophanmicrowaveassistedsynthesisandinvitrostudiesagainstifusariumoxysporumi
AT sergiotorrescortes diastereomericiniisidialkyldithiocarbamatesderivedfromieichalconesandʟtryptophanmicrowaveassistedsynthesisandinvitrostudiesagainstifusariumoxysporumi
AT ericssoncoybarrera diastereomericiniisidialkyldithiocarbamatesderivedfromieichalconesandʟtryptophanmicrowaveassistedsynthesisandinvitrostudiesagainstifusariumoxysporumi
AT ivonbuitrago diastereomericiniisidialkyldithiocarbamatesderivedfromieichalconesandʟtryptophanmicrowaveassistedsynthesisandinvitrostudiesagainstifusariumoxysporumi
AT diegoquiroga diastereomericiniisidialkyldithiocarbamatesderivedfromieichalconesandʟtryptophanmicrowaveassistedsynthesisandinvitrostudiesagainstifusariumoxysporumi