Synthesis and Anti-Inflammatory Evaluation of a Library of Chiral Derivatives of Xanthones Conjugated with Proteinogenic Amino Acids

last updated: 2023-08-04
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TitleSynthesis and Anti-Inflammatory Evaluation of a Library of Chiral Derivatives of Xanthones Conjugated with Proteinogenic Amino Acids
Publication TypePapers in Scientific Journals
Year of Publication2023
AuthorsVieira S. F., Araújo J., Gonçalves V. M. F., Fernandes C., Pinto M. M., Ferreira H., Neves N. M., and Tiritan M. E.
EditorsPibiri I.
Abstract

In recent decades, the relationship between drug chirality and biological activity has been assuming enormous importance in medicinal chemistry. Particularly, chiral derivatives of xanthones (CDXs) have interesting biological activities, including enantioselective anti-inflammatory activity. Herein, the synthesis of a library of CDXs is described, by coupling a carboxyxanthone (1) with both enantiomers of proteinogenic amino esters as chiral building blocks (231), following the chiral pool strategy. The coupling reactions were performed at room temperature with good yields (from 44 to 99.9%) and very high enantiomeric purity, with most of them presenting an enantiomeric ratio close to 100%. To afford the respective amino acid derivatives (3261), the ester group of the CDXs was hydrolyzed in mild alkaline conditions. Consequently, in this work, sixty new derivatives of CDXs were synthetized. The cytocompatibility and anti-inflammatory activity in the presence of M1 macrophages were studied for forty-four of the new synthesized CDXs. A significant decrease in the levels of a proinflammatory cytokine targeted in the treatment of several inflammatory diseases, namely interleukin 6 (IL-6), was achieved in the presence of many CDXs. The amino ester of L-tyrosine (X1AELT) was the most effective in reducing IL-6 production (52.2 ± 13.2%) by LPS-stimulated macrophages. Moreover, it was ≈1.2 times better than the D-enantiomer. Indeed, enantioselectivity was observed for the majority of the tested compounds. Thus, their evaluation as promising anti-inflammatory drugs should be considered.

JournalInternational Journal of Molecular Sciences
Volume24
Issue12
Pagination1-36
Date Published2023-06-19
PublisherMDPI
ISSN1422-0067
DOI10.3390/ijms241210357
URLhttps://www.mdpi.com/1422-0067/24/12/10357
KeywordsAnti-inflammatory activity, chiral pool, chirality, Enantioselectivity, xanthones
RightsopenAccess
Peer reviewedyes
Statuspublished

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