[Zurück]

T. Linder, R. Liu, A Atanasov, S. Geyrhofer, S. Schwaiger, H. Stuppner, M. Schnürch, V. Dirsch, M.D. Mihovilovic:
"Leoligin-inspired synthetic lignans with selectivity for cell-type and bioactivity relevant for cardiovascular disease";
Chemical Science, 10 (2019), S. 5815 - 5820.

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

http://dx.doi.org/10.1039/c9sc00446g

https://publik.tuwien.ac.at/files/publik_287292.pdf