One-pot semi-synthesis and neurogenic potential of pyranoflavonoids with different structural scaffolds

Flavonoids and chalcones show a variety of effects in the central nervous system, such as anti-inflammatory and antidepressant effects, as well as promoting neuronal differentiation, neurite outgrowth and nerve regeneration [1]. Such neurogenic effects have been demonstrated for the class of pyranochalcones [2]. Our question was whether other flavonoid scaffolds with a pyrano-ring as a structural moiety would also have comparable neurogenic potential.

Starting from the prenylated chalcone xanthohumol isolated from hops, pyranoflavanoids with different scaffolds (flavanone, flavone, flavonol and aurone) were obtained using several semi-synthetic approaches. The yields of the semi-synthesis were improved by microwave irradiation and a less toxic reagent than usually applied for aurone synthesis could be used. The different semi-synthetic isomerisation reactions are well suited for further structure-activity studies of natural products as they are mostly simple one-pot, one- step reactions that provide a readily accessible source of different flavonoid scaffolds. Furthermore, using a reporter gene assay based on the promoter activity of doublecortin, an early neuronal marker, we identified the chalcone scaffold as the most active scaffold with pyrano-ring. Accordingly, pyranochalcones remain a promising class of compounds to develop a strategy for treating neurodegenerative diseases.

• References

• 1 Spencer JP.. The interactions of flavonoids within neuronal signalling pathways. Genes Nutr 2007; 2: 257-273
• 2 Oberbauer E, Urmann C, Steffenhagen C, Bieler L, Brunner D, Furtner T, Humpel C, Baumer B, Bandtlow C, Couillard-Despres S, Rivera FJ, Riepl H, Aigner L.. Chroman-like cyclic prenylflavonoids promote neuronal differentiation and neurite outgrowth and are neuroprotective. J Nutr Biochem 2013; 24: 1953-1962

Publication History

Article published online:
16 November 2023