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

Autor:	Thomas Linder, Michael Schnürch, Atanas G. Atanasov, Sophie Geyrhofer, Rongxia Liu, Marko D. Mihovilovic, Yuanfang Li, Hermann Stuppner, Verena M. Dirsch, Stefan Schwaiger
Rok vydání:	2019
Předmět:	Lignan Neointima Cell type Vascular smooth muscle 010405 organic chemistry Context (language use) Biological activity General Chemistry 010402 general chemistry 01 natural sciences 0104 chemical sciences Endothelial stem cell chemistry.chemical_compound Biochemistry chemistry Selectivity
Zdroj:	Chemical Science. 10:5815-5820
ISSN:	2041-6539 2041-6520
DOI:	10.1039/c9sc00446g
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6b3ad6c0a2e27caa7a6b37da5397ab8e https://doi.org/10.1039/c9sc00446g Zobrazit plný text záznamu