Leoligin-inspired synthetic lignans with selectivity for cell-type and bioactivity relevant for cardiovascular disease

Linder, Thomas; Liu, Rongxia; Atanasov, Atanas G.; Li, Yuanfang; Geyrhofer, Sophie; Schwaiger, Stefan; Stuppner, Hermann; Schnurch, Michael; Dirsch, Verena M. und Mihovilovic, Marko D. (2019): Leoligin-inspired synthetic lignans with selectivity for cell-type and bioactivity relevant for cardiovascular disease. In: Chemical Science, Bd. 10, Nr. 22: S. 5815-5820

Abstract

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-kappa B pathway. Results are discussed in the context of structural modification of these novel synthetic lignans.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2041-6520
• Sprache: Englisch