Yuccalechins A-C from the Yucca schidigera Roezl ex Ortgies Bark: Elucidation of the Relative and Absolute Configurations of Three New Spirobiflavonoids and Their Cholinesterase Inhibitory Activities.

Pecio Pecio,Orhan Orhan,Deniz Deniz,Eren Eren,Alilou Alilou,Stuppner Stuppner,Oleszek Oleszek

doi:10.3390/molecules24224162

Abstract

The ethyl acetate fraction of the methanolic extract of Yucca schidigera Roezl ex Ortgies bark exhibited moderate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity (IC50 47.44 and 47.40 µg mL−1, respectively). Gel filtration on Sephadex LH-20 and further RP-C18 preparative HPLC of EtOAc fraction afforded 15 known and 3 new compounds, stereoisomers of larixinol. The structures of the isolated spirobiflavonoids 15, 26, and 29 were elucidated using 1D and 2D NMR and MS spectroscopic techniques. The relative configuration of isolated compounds was assigned based on coupling constants and ROESY (rotating-frame Overhauser spectroscopy) correlations along with applying the DP4+ probability method in case of ambiguous chiral centers. Determination of absolute configuration was performed by comparing calculated electronic circular dichroism (ECD) spectra with experimental ones. Compounds 26 and 29, obtained in sufficient amounts, were evaluated for activities against AChE and BChE, and they showed a weak inhibition only towards AChE (IC50 294.18 µM for 26, and 655.18 µM for 29). Furthermore, molecular docking simulations were performed to investigate the possible binding modes of 26 and 29 with AChE.

Highlights

These products possess the generally recognized as safe (GRAS) label given by the FDA, which allows human dietary use
There are several publications mentioning a wide variety of phenolic compounds present in the bark of the plant byproducts of Y. schidigera in commercial applications [7,8,9,10]
Identification of the Constituents Found in the Y. schidigera Ethyl Acetate Fraction

Summary

Introduction

Derivatives of trans-resveratrol (trans-3,40 ,5-trihydroxystilbene) and trans-3,30 ,5,50 -tetrahydroxy-40 -methoxystilbene, such as yuccaols A–E and yuccaone A, which are unique spiro-compounds including C15 and C14 units condensed to form a γ-lactone ring, very rarely occur in the plant kingdom [11]. These compounds are known for their various antioxidant, radical scavenging, inhibiting iNOS expression, and platelet aggregation activities in vitro [7,12]. Another four new spirobiflavonoids, named olgensisinols A–D, along with a known one, vitisinol, were isolated from the stem bark of L. olgensis HENRY var. koreana NAKAI [18], two new spirobiflavonoids from Abies chensiensis (3-epi-larixinol and 3,20 -epi-larixinol) [19], and six from A. sachalinensis [20]

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