caa a22 4500 445878908 CHVBK 20180317145536.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11030-010-9280-3 doi (NATIONALLICENCE)springer-10.1007/s11030-010-9280-3 First computational chemistry multi-target model for anti-Alzheimer, anti-parasitic, anti-fungi, and anti-bacterial activity of GSK-3 inhibitors in vitro, in vivo, and in different cellular lines [Elektronische Daten] [Isela García, Yagamare Fall, Generosa Gómez, Humberto González-Díaz] In the work described here, we developed the first multi-target quantitative structure-activity relationship (QSAR) model able to predict the results of 42 different experimental tests for GSK-3 inhibitors with heterogeneous structural patterns. GSK-3β inhibitors are interesting candidates for developing anti-Alzheimer compounds. GSK-3β are also of interest as anti-parasitic compounds active against Plasmodium falciparum, Trypanosoma brucei, and Leishmania donovani; the causative agents for Malaria, African Trypanosomiasis and Leishmaniosis. The MARCH-INSIDE technique was used to quickly calculate total and local polarizability, n-octanol/water partition coefficients, refractivity, van der Waals area and electronegativity values to 4,508 active/non-active compounds as well as the average values of these indexes for active compounds in 42 different biological assays. Both the individual molecular descriptors and the average values for each test were used as input for a linear discriminant analysis (LDA). We discovered a classification function which used in training series correctly classifies 873 out of 1,218 GSK-3 cases of inhibitors (97.4%) and 2,140 out of 2,163 cases of non-active compounds (86.1%) in the 42 different tests. In addition, the model correctly classifies 285 out of 406 GSK-3 inhibitors (96.3%) and 710 out of 721 cases of non-active compounds (85.4%) in external validation series. The result is important because, for the first time, we can use a single equation to predict the results of heterogeneous series of organic compounds in 42 different experimental tests instead of developing, validating, and using 42 different QSAR models. Lastly, a double ordinate Cartesian plot of cross-validated residuals (first ordinate), standard residuals (second ordinate), and leverages (abscissa) defined the domain of applicability of the model as a squared area within ±2 band for residuals and a leverage threshold of h =0.0044. Springer Science+Business Media B.V., 2010 Glycogen synthase kinase-3 (GSK-3) inhibitors nationallicence Alzheimer's disease nationallicence Malaria nationallicence Plasmodium falciparum nationallicence Trypanosomiasis nationallicence Trypanosoma brucei nationallicence QSAR nationallicence Markov Model nationallicence Linear discriminant analysis nationallicence García Isela Department of Organic Chemistry, University of Vigo, Vigo, Spain aut Fall Yagamare Department of Organic Chemistry, University of Vigo, Vigo, Spain aut Gómez Generosa Department of Organic Chemistry, University of Vigo, Vigo, Spain aut González-Díaz Humberto Department of Microbiology and Parasitology, Faculty of Pharmacy, USC, 15782, Santiago de Compostela, Spain aut Molecular Diversity Springer Netherlands 15/2(2011-05-01), 561-567 1381-1991 15:2<561 2011 15 11030 https://doi.org/10.1007/s11030-010-9280-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-010-9280-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- García Isela Department of Organic Chemistry, University of Vigo, Vigo, Spain aut NATIONALLICENCE 700 1- Fall Yagamare Department of Organic Chemistry, University of Vigo, Vigo, Spain aut NATIONALLICENCE 700 1- Gómez Generosa Department of Organic Chemistry, University of Vigo, Vigo, Spain aut NATIONALLICENCE 700 1- González-Díaz Humberto Department of Microbiology and Parasitology, Faculty of Pharmacy, USC, 15782, Santiago de Compostela, Spain aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/2(2011-05-01), 561-567 1381-1991 15:2<561 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer