A QSAR toxicity study of a series of alkaloids with the lycoctonine skeleton.
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 bidescriptor models (when combined with lipophilicity, MlogP) confirming the importance of H-bonding capability of the alkaloids for binding at the receptor site.
Turabekova
Malakhat A
MA
Institute of Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Kh. Abdullaev Str., 77, Tashkent, 700170, Uzbekistan. malohathon@yahoo.com
Rasulev
Bakhtiyor F
BF
D000157:Aconitine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D031841:Aconitum / Q000737:chemistry / Q000235:genetics / Q000633:toxicity; D000465:Algorithms; D000470:Alkaloids / Q000737:chemistry* / Q000633:toxicity*; D002627:Chemistry, Physical / Q000379:methods / Q000706:statistics & numerical data; D031882:Delphinium / Q000737:chemistry / Q000235:genetics / Q000633:toxicity; D016014:Linear Models; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
D000470:Alkaloids; C093992:lycoctonine; D000157:Aconitine