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Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9′ Derivatisation

Dibenzylbutyrolactone lignans (DBLs) are a class of natural products with a wide variety of biological activities. Due to their potential for the development of human therapeutic agents, DBLs have been subjected to various SAR studies in order to optimise activity. Previous reports have mainly consi...

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Detalles Bibliográficos
Autores principales: Paulin, Emily K., Leung, Euphemia, Pilkington, Lisa I., Barker, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866048/
https://www.ncbi.nlm.nih.gov/pubmed/36674683
http://dx.doi.org/10.3390/ijms24021167
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author Paulin, Emily K.
Leung, Euphemia
Pilkington, Lisa I.
Barker, David
author_facet Paulin, Emily K.
Leung, Euphemia
Pilkington, Lisa I.
Barker, David
author_sort Paulin, Emily K.
collection PubMed
description Dibenzylbutyrolactone lignans (DBLs) are a class of natural products with a wide variety of biological activities. Due to their potential for the development of human therapeutic agents, DBLs have been subjected to various SAR studies in order to optimise activity. Previous reports have mainly considered changes on the aromatic rings and at the benzylic carbons of the compounds, whilst the effects of substituents in the lactone, at the C-9′ position, have been relatively unexplored. This position has an unexploited potential for the development of novel dibenzyl butyrolactone derivatives, with previous preliminary findings revealing C-9′-hydroxymethyl analogues inducing programmed cell cycle death. Using the core structure of the bioactive natural product arctigenin, C-9′ derivatives were synthesised using various synthetic pathways and with prepared derivatives providing more potent anti-proliferative activity than the C-9′-hydroxymethyl lead compound.
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spelling pubmed-98660482023-01-22 Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9′ Derivatisation Paulin, Emily K. Leung, Euphemia Pilkington, Lisa I. Barker, David Int J Mol Sci Article Dibenzylbutyrolactone lignans (DBLs) are a class of natural products with a wide variety of biological activities. Due to their potential for the development of human therapeutic agents, DBLs have been subjected to various SAR studies in order to optimise activity. Previous reports have mainly considered changes on the aromatic rings and at the benzylic carbons of the compounds, whilst the effects of substituents in the lactone, at the C-9′ position, have been relatively unexplored. This position has an unexploited potential for the development of novel dibenzyl butyrolactone derivatives, with previous preliminary findings revealing C-9′-hydroxymethyl analogues inducing programmed cell cycle death. Using the core structure of the bioactive natural product arctigenin, C-9′ derivatives were synthesised using various synthetic pathways and with prepared derivatives providing more potent anti-proliferative activity than the C-9′-hydroxymethyl lead compound. MDPI 2023-01-06 /pmc/articles/PMC9866048/ /pubmed/36674683 http://dx.doi.org/10.3390/ijms24021167 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Paulin, Emily K.
Leung, Euphemia
Pilkington, Lisa I.
Barker, David
Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9′ Derivatisation
title Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9′ Derivatisation
title_full Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9′ Derivatisation
title_fullStr Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9′ Derivatisation
title_full_unstemmed Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9′ Derivatisation
title_short Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9′ Derivatisation
title_sort synthesis and anti-proliferative evaluation of arctigenin analogues with c-9′ derivatisation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866048/
https://www.ncbi.nlm.nih.gov/pubmed/36674683
http://dx.doi.org/10.3390/ijms24021167
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