Letters in Drug Design & Discovery, 2011, 8, ???-??? 1 1570-1808/11 $58.00+.00 © 2011 Bentham Science Publishers Ltd. In Silico Studies of (2E,5E)-2,5-bis(3-methoxy-4-hydroxy-benzylidene) Cyclopentanone on Proteins AChE and BChE Involved in Alzheimer's disease and Ameliorative Effects on Paraquat Induced Oxidative Stress Markers in Drosophila melanogaster Balladka Kunhanna Sarojini* ,a , Chenna Govindaraju Darshan Raj a , Modalkoppalu Kyathegowda Ramakrishna b , Saraf R Ramesh b , Basavapattana Rudresh Bharath c and Hanumanthappa Manjunatha c a Department of Chemistry, P. A. College of Engineering, Nadupadavu, Mangalore - 574153, Karnataka, India b DST Unit on Evolution and Genetics & Drosophila Stock Centre, Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore-570006 Karnataka, India c Department of P.G. Studies and Research in Biotechnology and Bioinformatics, Jnanasahyadri, Kuvempu University, Shankaraghatta-577451, Karnataka, India Received June 28, 2010: Revised October 14, 2010: Accepted December 07, 2010 Abstract: In the present study, the ameliorative effect of a bischalcone (2E,5E)-2,5-bis(3-methoxy-4-hydroxy- benzylidene) cyclopentanone (CA), a curcumin analog was studied on Drosophila melanogaster (oregon K strain) in vivo by inducing oxidative stress using paraquat. Curcumin (CU) was taken as standard for studies. In negative geotaxis assay it was found that CA was able to rescue the flies significantly from deteriorating locomotor dysfunctions. A docking study for antialzeimer’s activity of CA was carried out by targeting the proteins Acetylcholinesterase (AChE) and Butyrylcho- linesterase (BChE). It binds effectively to the target proteins. Keywords: Antioxidant, Alzheimer disease, Bischalcone, Paraquat, Molecular docking, Oxidative stress. INTRODUCTION Neurodegenerative disorders remain an important source of morbidity and suffering for the mankind. The role of free- radical-mediated oxidative injury in acute insults to the nervous system including stroke or trauma, as well as in chronic neurodegenerative disorders, is well recognized. It is known that, oxygen is an essential molecule for survival of majority of living organisms. Oxidative stress is a harmful condition that occurs when there is an excess of free radicals and/or a decrease in antioxidant levels. The evidence to date for oxidative stress in Parkinson’s disease (PD), Schizophre- nia (SCZ), Alzheimer's disease (AD) and other neurodegen- erative diseases is strongly persuasive. Clinical studies showed that a number of events associated with Alzheimer’s are capable of stimulating production of free radicals and depletion of antioxidant levels. As pointed out, whether oxi- dative stress is eventually proven to be primary or secondary in etiologic progression, the therapeutic rewards of antioxi- dants are likely to be substantial. Clearly, strategies aimed at limiting free radical induced oxidative stress and damage may slow the progression of neurodegenerative diseases [1]. Paraquat (1,1-dimethyl-4,4-bipyridynium dichloride) is a quaternary nitrogen herbicide and highly toxic substance for humans and animals; many cases of acute poisoning and death have been reported [2]. The toxicity of paraquat is due *Address correspondence to this author at the Department of Chemistry, P. A. College of Engineering, Nadupadavu, Mangalore - 574153, Karnataka, India; Tel: + 91 824 2284701/2/3; Fax: + 91 824 2284705; E-mails: bksaroj@yahoo.com, bksaroj35@gmail.com, darshanraj22@gmail.com to the generation of the superoxide anion which can lead to the synthesis of more toxic reactive oxygen species (ROS) such as hydroxyl radicals and hydrogen peroxide [3]. On the other hand, the oxidation of reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) as a consequence of paraquat administration results in the disruption of bio- chemical processes requiring NADPH [4]. The oxidative stress caused by free radicals contributes to the development of Alzheimer's disease. AD is the most common form of dementia in adults, which is characterized by senile plaques and cholinergic deficit as the disease pro- gresses. Improvement of cholinergic neurotransmission is the basis of some drugs currently used in the treatment of AD. It is achieved by AChE inhibition, the enzyme re- sponsible for acetylcholine hydrolysis. Molecular modeling techniques are of utmost importance to design a new phar- maceutical agent against Alzheimer's disease, with potential inhibitory activity over AChE. Some of the drugs currently used in the treatment of AD are capable of increasing the cholinergic transmission through the AChE inhibition and also the inhibition of human plasma BChE [5]. Curcumin, commonly called diferuloyl methane, is a hy- drophobic polyphenol derived from the rhizome (turmeric) of the herb Curcuma longa. It exhibits antioxidant, anti- inflammatory, antimicrobial, and anticarcinogenic activities. In spite of its efficacy and safety, curcumin has not yet been approved as a therapeutic agent. The poor aqueous solubility, relatively low bioavailability and intense staining color of curcumin were highlighted as major problems; and conse- quently search for a ‘‘super curcumin’’ without these prob-