ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

MTD-PLS and docking study for a series of substituted 2-phenylindole derivatives with oestrogenic activity

Edward Seclaman, Alina Bora, Sorin Avram, Zeno Simon, and Ludovic Kurunczi

University of Medicine and Pharmacy “Victor Babes” Timisoara, Eftimie Murgu 2, 300041 Timisoara, Romania

E-mail: kurunczi@umft.ro

Abstract: A series of 36 substituted 2-phenylindoles was analysed using minimal topological difference-projections in latent structures variant (MTD-PLS) and molecular docking, using fast rigid exhaustive docking (FRED) and AutoDock Vina programs. For quantitative structure activity relationships (QSAR) validation, a sphere exclusion algorithm in the multi-dimensional descriptor space was used to construct training and test sets. Docking procedures were based on X-ray crystallography studies using the human alpha oestrogen receptor-17β-oestradiol complex. The ranking abilities of the different scoring functions of the FRED package were presented, and the most suitable scoring function (Chemgauss3) for the oestrogen receptor was chosen. Although the series studied contains only a limited number of compounds, the MTD-PLS method and the docking procedure provided coherent results in concordance with the X-ray diffraction data for different ligand-oestrogen receptor complexes.

Keywords: MTD-PLS method – molecular docking – FRED – 2-phenylindole derivatives

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-011-0040-3

Chemical Papers 65 (4) 566–576 (2011)