Recently, a natural compound leoligin, a furan-type lignan, was discovered as an interesting hit compound with an anti-inflammatory pharmacological activity profile. We developed a modular and stereoselective approach for the synthesis of the edelweiss-derived lignan leoligin and used the synthetic route to rapidly prepare leoligin analogs even on the gram scale. Proof of concept of this approach together with cell-based bio-assays gained structural analogs with increased selectivity towards vascular smooth muscle versus endothelial cell proliferation inhibition, a major benefit in fighting vascular neointima formation. In addition, we identified the structural features of leoligin analogs that define their ability to inhibit the pro-inflammatory NF-κB pathway. Results are discussed in the context of structural modification of these novel synthetic lignans.
Leoligin-inspired synthetic lignans with selectivity for cell-type and bioactivity relevant for cardiovascular disease. Thomas Linder, Rongxia Liu, Atanas G. Atanasov, Yuanfang Li, Sophie Geyrhofer, Stefan Schwaiger, Hermann Stuppner, Michael Schnürch, Verena M. Dirsch, Marko D. Mihovilovic. Chem. Sci., 2019,10, 5815-5820
Keywords: leoligin, synthetic lignans, bioactivity relevant for cardiovascular disease, anti-inflammatory pharmacological activity, edelweiss, synthesis, vascular smooth muscle cells, endothelial cells, proliferation inhibition, neointima, NF-κB inhibition.
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