ASIAN JOURNAL OF CHEMISTRY ASIAN JOURNAL OF CHEMISTRY http://dx.doi.org/10.14233/ajchem.2014.17001 INTRODUCTION Alzheimer’s disease (AD) is a chronic neurological disorder characterized by memory impairment, cognitive dysfunction and behavioral disturbances 1,2 . Alzheimer’s disease has been found to be associated with a cholinergic deflcit in the post-mortem brain characterized by a significant decrease in acetylcholine content 3,4 . Acetylcholine is a neurotransmitter inhibited primarily by acetylcholinesterase (AChE) and secondly by butyrylcholine- sterase (BChE) and is considered to play a role in the pathology of Alzheimer’s disease 5 . Despite the unknown etiology of Alzheimer’s disease, elevation of acetylcholine amount through AChE enzyme inhibition has been accepted as the most effective treatment strategy against Alzheimer’s disease 6 . It has been found that BChE is found in significantly higher quantities in Alzheimer plaques than in plaques of normal age-related non-demented brains. It is generally viewed as a backup for the homologous acetylcholinesterase and to act as a scavenger for anticholine- sterase compounds 7 . Therefore, AChE and BChE inhibitors have become the remarkable alternatives in treatment of Alzheimer’s disease. However, the present drugs with AChE inhibitory activity have some side effects and are effective only against the mild type of Alzheimer’s disease 8 . Consequently, it is compulsory to develop new drugs in order to combat Alzheimer’s disease. Cholinesterase Inhibitory Triterpenes from Perovskia atriplicifolia S. PERVEEN 1 , A.M. AL-TAWEEL 1 , G.A. FAWZY 1,2,* , T.A. IBRAHIM 1,2 , A. MALIK 3 and A. KHAN 4 1 Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, P.O. Box 2457, Riyadh 11451, Saudi Arabia 2 Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt 3 International Centre for Chemical and Biological Sciences, H.E.J. Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan 4 Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad-22060, Pakistan *Corresponding author: Fax: +966 1 12914842; Tel: +966 1 18050496; E-mail: gzeineldin@outlook.com; gfewzy@ksu.edu.sa Received: 7 January 2014; Accepted: 20 February 2014; Published online: 1 September 2014; AJC-15875 Nine compounds including β-amyrin (1), erythrodiol (2), oleanolic acid (3), 3β-hydroxy-11,13(18)-oleanadien-28-oic acid (4), glycyrrhetinic acid (5), 2α,3β-dihydroxyolean-12-en-28-methyl ester (6), 2α,3β-dihydroxyolean-12-en-28-oic acid (7), 2α,3β,24-trihydroxyolean-12- en-28-oic acid (8) and 2α,3β,19β-trihydroxyurs-12-en-28-oic acid (9), have been isolated from Perovskia atriplicifolia. Their structures have been established with the help of different spectral data. All of these compounds were tested for cholinesterase inhibitory activity. Among the tested compounds, 8 and 9 were found to be the most active against both enzymes, with a significant butyrylcholinesterase (BChE) inhibitory activity demonstrating IC50 values 9.50 and 13.52 mM, respectively, compared to galanthamine standard (IC50: 8.51 mM). Keywords: Cholinesterase inhibition, Lamiaceae, Perovskia atriplicifolia, Triterpenes. Genus Perovskia belongs to family Lamiaceae and com- prises seven species, one of which is Perovskia atriplicifolia, commonly known as Russian sage. The plant is shrubby, found in Central Asia, Pakistan, Afghanistan and Iran. P. atriplicifolia has antibacterial activity and is also used as cooling medicine in the treatment of fever 9 . Many compounds have been previously reported from this species 10 . The ethnopharma- cological and chemotaxanomic importance of the genus Perovskia prompted us to do further investigation of the chemical constituents of P. atriplicifolia. Moreover, pharmaco- logical screening revealed significant cholinesterase inhibitory activity in the chloroform soluble fraction of the plant. Bioassay directed isolation studies on this fraction resulted in the isolation of triterpenes 1-9. EXPERIMENTAL General procedure: Column chromatography (CC): Silica gel 70-230 mesh; TLC: pre-coated silica gel 60 F254 (20 × 20 cm, 0.2 mm thick; E-Merck) plates; UV: detection at 254 nm and using ceric sulphate reagent. Optical rotations: Jasco- DIP-360 digital polarimeter. IR spectra: Shimadzu IR-460 spectrophotometer. 1 H NMR spectra: Bruker spectrometers operating at 300, 400 and 500 MHz. Chemical shift δ in ppm relative to SiMe4 as internal standard and coupling constants Asian Journal of Chemistry; Vol. 26, No. 18 (2014), 6163-6166