Potent and selective butyrylcholinesterase inhibitors from Ficus foveolata Thiendanai Sermboonpaisarn a, b , Pattara Sawasdee a, ⁎ a Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Bangkok 10330, Thailand b Center for Petroleum, Petrochemicals and Advanced Materials, Chulalongkorn University, 254 Phayathai Road, Bangkok 10330, Thailand article info abstract Article history: Received 4 November 2011 Received in revised form 5 March 2012 Accepted 7 March 2012 Available online 16 March 2012 Four stilbenes (1–4), one inseparable mixture of two alkyl diferulates (5a, 5b), one alkyl ferulate (6) and four flavonoids (7–10) were isolated from Ficus foveolata Wall. Except for quercetin (10), the other ten constituents were isolated from F. foveolata for the first time. In addition, one of the two components in mixture 5 is a new compound identified as (1E,22E)-1,22-docosanediol difer- ulate (5a). All nine isolated compounds, plus the mixture of 5a and 5b known as 5, exhibited a low or no activity against acetylcholinesterase. However, and interestingly, the stilbenes 1–4 showed a high inhibition towards butyrylcholinesterase. Gnetol (4) had the lowest IC 50 value of 1.3 μM towards butyrylcholinesterase and showed a reversible and competitive inhibition in the kinetic study. © 2012 Elsevier B.V. All rights reserved. Keywords: Ficus foveolata Moraceae Stilbenes Gnetols Acetylcholinesterase Butyrylcholinesterase 1. Introduction Ficus foveolata (Wall. ex Miq.), in the family Moraceae, (syn. Ficus sarmentosa Buch.-Ham. Ex Sm.), is a rare medic- inal plant that is distributed mainly in the North and North- eastern part of Thailand. Native Thai people drink the alcoholic macerated F. foveolata vines as a rejuvenating agent and a tonic for enhancing their sexual performance [1]. The genus Ficus is comprised of over 800 recognized species and previous works on this genus have led to the isolation of many compounds from several different classes (e.g. triterpenoids, alkaloids, flavonoids and stilbenes) [2–4]. However, to the best of our knowledge, until now only three publications have reported the phytochemical constituents of F. sarmentosa var. henryi [5–7]. In these re- ports, several flavonoids, e.g. apigenin, quercetin, luteolin and kaempferol, together with 7-methoxycoumarin were obtained and some of them showed significant antifungal and insecticidal activities [5–7]. However, the polar compo- nents of this species have not been explored. Our interest in this plant was raised when we performed an anti-cholinesterase (anti-ChE) screen of plant extracts against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the causal enzymes of Alzheimer's disease (AD). Amongst the most potent extracts found in this screen was the methanolic extract of F. foveolata vines, which inhibited BChE by 91% at a test concentration of 100 μg/mL. Herein, we report the isolation and structure elucidation of one new com- pound, (1E,22E)-1,22-docosanediol diferulate (5a), which was found as an inseparable mixture with (1E,24E)-1,24-tetracosa- nediol diferulate (5b), together with that for nine other already known compounds, resveratrol (1), isorhapontigenin (2), pinosylvin (3), gnetol (4), 24′-hydroxy-tetracosyl ferulate (6), galangin 3-methyl ether (7), tectochrysin (8), 5- hydroxy-3,7-dimethoxyflavone (9) and quercetin (10) (Fig. 1). These were isolated from the less-polar (CH 2 Cl 2 ) and more-polar (BuOH) fractions. Except for quercetin (10), the other constituents were isolated from F. foveolata for the first time. The anti-ChE activity, in terms of separate AChE and BChE activities, of all ten isolated compounds was examined and it was found that gnetol (4) showed the most selective BChE inhibition. Fitoterapia 83 (2012) 780–784 ⁎ Corresponding author. Tel.: + 66 2 2187624; fax: + 66 2 2187598. E-mail address: p_tiew@hotmail.com (P. Sawasdee). 0367-326X/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.fitote.2012.03.009 Contents lists available at SciVerse ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote