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. 2021 Dec 28;10(1):62.
doi: 10.3390/biomedicines10010062.

Investigation of Leoligin Derivatives as NF-κΒ Inhibitory Agents

Thomas Linder  1 , Eleni Papaplioura  1 , Diyana Ogurlu  2 , Sophie Geyrhofer  1 , Scarlet Hummelbrunner  2 , Daniel Schachner  2 , Atanas G Atanasov  2   3   4 , Marko D Mihovilovic  1 , Verena M Dirsch  2 , Michael Schnürch  1
Affiliations

Investigation of Leoligin Derivatives as NF-κΒ Inhibitory Agents

Thomas Linder et al. Biomedicines. .

Abstract

The transcription factor NF-κB is an essential mediator of inflammation; thus, the identification of compounds that interfere with the NF-κB signaling pathway is an important topic. The natural products leoligin and 5-methoxyleoligin have served as a starting point for the development of NF-κB inhibitors. Using our modular total synthesis method of leoligin, modifications at two positions were undertaken and the effects of these modifications on the biological activity were investigated. The first modification concerned the ester functionality, where it was found that variations in this position have a significant influence, with bulky esters lacking Michael-acceptor properties being favored. Additionally, the substituents on the aryl group in position 2 of the tetrahydrofuran scaffold can vary to some extent, where it was found that a 3,4-dimethoxy and a 4-fluoro substitution pattern show comparable inhibitory efficiency.

Keywords: NF-κB inhibition; inflammation; lignans; natural product synthesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of leoligin.
Scheme 1
Scheme 1
Synthesis of cyclohexenyl derivative 3.
Scheme 2
Scheme 2
Synthesis of para-fluoro derivative 14.
Scheme 3
Scheme 3
General scheme for Steglich and Mitsunobu esterification.
Figure 2
Figure 2
Structures of leoligin and 5-methoxyleoligin.
See this image and copyright information in PMC

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