qsar studies on n-aryl derivative activity towards alzheimer’s disease构象研究n-aryl导数活动对阿尔茨海默氏症.pdfVIP

Molecules 2009, 14, 1448-1455; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article QSAR Studies on N-aryl Derivative Activity Towards Alzheimer’s Disease Kamalakaran Anand Solomon *, Srinivasan Sundararajan and Veluchamy Abirami Department of Bioinformatics, Sri Ramachandra University, No.1.Ramachandra Nagar, Porur, Chennai- 600116, India * Author to whom correspondence should be addressed: Email: anand.dcb@. Received: 16 March 2009; in revised form: 1 April 2009 / Accepted: 2 April 2009 / Published: 7 April 2009 Abstract: A Quantitative Structure Activity Relationship (QSAR) study has been an attempted on a series of 88 N-aryl derivatives which display varied inhibitory activity towards both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), targets in Alzheimer’s drug discovery. QSAR models were derived for 53 and 61 compounds for each target, respectively, with the aid of genetic function approximation (GFA) technique using topological, molecular shape, electronic and structural descriptors. The predictive ability of the QSAR model was evaluated using a test set of 26 compounds for AChE (r2 pred = 0.857), (q2 = 0.803) and 20 compounds for BChE (r2 pred = 0.882), (q2 = 0.857). The QSAR models point out that AlogP98, Wiener, Kappa-1-AM, Dipole-Mag, and CHI-1 are the important descriptors effectively describing the bioactivity of the compounds. Keywords: N-aryl derivat