a qsar toxicity study of a series of alkaloids with the lycoctonine skeleton构象毒性研究的一系列生物碱lycoctonine骨架.pdfVIP

Molecules 2004, 9, 1194-1207 molecules ISSN 1420-3049 A QSAR Toxicity Study of a Series of Alkaloids with the Lycoctonine Skeleton Malakhat A. Turabekova 1,2,* and Bakhtiyor F. Rasulev 1 1 Institute of Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Kh. Abdullaev Str., 77, Tashkent, 700170, Uzbekistan. Tel. (+998) 71-1627897, Fax (+998) 71- 1206475 2 Chemistry Department, National University of Uzbekistan named after Mirzo Ulugbek, Vuzgorodok, Tashkent, 700174, Uzbekistan. Tel. (+998) 71-2460788, Fax (+998) 71-1447728 * Author to whom correspondence should be addressed; Email: malohathon@ Received: 26 April 2004 / Accepted: 10 August 2004 / Published: 31 December 2004 Abstract : A QSAR toxicity analysis has been performed for a series of 19 alkaloids with the lycoctonine skeleton. GA-MLRA (Genetic Algorithm combined with Multiple Linear Regression Analysis) technique was applied for the generation of two types of QSARs: first, models containing exclusively 3D-descriptors and second, models consisting of physicochemical descriptors. As expected, 3D-descriptor QSARs have better statistical fits. Physicochemical-descriptor containing models, that are in a good agreement with the mode of toxic action exerted by the alkaloids studied, have also been identified and discussed. In particular, TPSA (Topological Polar Surface Area) and nC=O (number of –C(O)– fragments) parameters give the best statistically significant mono- and