Sulphated flavonoid isolated from Flaveria bidentis and its semisynthetic derivatives as potential drugs for Alzheimer´s disease

Flavonoids are well-known natural compounds that attract increasing attention due to a wide range of pharmacological properties related to a variety of neurological disorders, like neuroprotective effect [1], acetylcholinesterase (AChE) inhibitory activity [2] and free radical scavenging ability [3], among others. Thus, the isolation from natural sources and semi-synthesis of new effective flavonoid derivatives are an interesting strategy for the research on anti-Alzheimer´s disease drugs. Flaveria bidentis (L.) Kuntze (Asteraceae), is an endemic species from Argentina. Potent AChE inhibitory activity was observed in its ethanolic extract (IC50=0.12 mg/mL). Partition with Hexane/H2O of this extract led to spontaneous crystallization of a sulphated flavonoid from the aqueous layer, with excellent yield. It´s structure was elucidated by HRMS and mono- and bidimensional NMR, and has been identified as 6-methoxykaempferol-3-sulphate (1). This is the first report of this flavonoid in F. bidentis. Compound 1 has been isolated previously only from F. chloraefolia [4], characterized just by UV spectroscopy. The present study is the first report of complete NMR and MS data of 1.In order to improve the moderate AChE inhibitory activity of 1, this compound has been submitted to chemical modifications which led to the semisynthethic desulphated, methylated, alkylated and acetylated analogs. These derivatives have been fully characterized by NMR and MS and are reported here for the first time. AChE inhibitory activity and scavenging of DPPH free radical of these derivatives will be discussed and compared to 1.