QSAR studies on imidazothienopyrazines as IKK‐β inhibitors: from 2D to 3D

Abstract

This paper presents the investigation of quantitative structure-activity relationship (QSAR) for imidazothienopyrazines from 2D to 3D, for assistance of developing new IKK-b inhibitors. In 2D-QSAR, we built linear and nonlinear models by heuristic method (HM) and Support Vector Machine (SVM) methods, respectively. The resultsshowed that the nonlinear model is more precise to predict the activities of imidazothienopyrazines. In 3D-QSAR, Phase methodology was employed, resulting in a successful model for prediction of imidazothienopyrazines' bioactivities, and this model (R 2 (training set) ¼ 0.9717, R 2 (test set) ¼ 0.9209) is better than any one of 2D-QSAR models, linear or nonlinear. In addition, the discussion of 2D descriptors from 2D-QSAR and the 3D plots from Phase results provided suggestions and guidance to develop new compounds which may present better bioactivities against IKK-b.

A Computational Study on Antimalarial Dispiro-1,2,4-Trioxolanes

“…MEP maps characterizes the region of the 1,2,4-trioxolane ring as a surface of negative electrostatic potential. The PCA and HCA methods make possible to classify the compounds studied (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) into two classes according to their degree of antimalarial activity against P. falciparum taking into account only three properties: BFE, logP and VOL. The regression model showed statistical significance and predictive ability.…”

“…13 14 Also it has been of great significance the use of quantitative structure-activity relationship (QSAR) for predicting new more potent molecules. [14][15][16][17][18][19][20][21][22][23] In a previous report on antimalarial artemisinin derivatives, MEP maps and molecular modeling have supported PLS results, revealing that higher values for HOMO energy combined with lower negative charge on oxygen atom, higher positive charge on carbon atom of the trioxane-ring system, higher values for the molecular volume and generally lower values for hydrophilic index increase antimalarial activity against P. falciparum. 16 Delivered by Ingenta to: Rice University IP: 5 In this work, the conformational search for dispiro-1,2,4-trioxolane (1) (Fig.…”

“…All used activities in this report are logarithms of 1/IC 50 (−logIC 50 = pIC 50 ). In this work the compounds were considered according to the following criteria: compounds with pIC 50 < 8 43 mol/L (3,8,9,12,14,15,16,18,19,20) are the least potent compounds while those with pIC 50 ≥ 8 43 mol/L (1,2,4,5,6,7,10,11,13,17) are the most potent compounds.…”

“…The left side contains samples with the lowest PC1 values (1,2,4,5,6,7,10,11,13,17), corresponding to the most active compounds. The right side contains samples with the highest PC1 values (3,8,9,12,14,15,16,18,19,20), corresponding to the lowest active compounds. The loadings for the two PCs are presented in Figure 5 and reveal the importance that these descriptors give to separate samples into two classes.…”

Chemometrics in China

“…The number of Chinese papers published in CEM gradually increased during the 1990s, accounting for five of the 49 papers published in1996. In the first decade of the millennium, this number reached a peak of nine Chinese papers among the total 68 research papers in 2009. In the current decade, there are 20 Chinese papers among the total 58 research papers in 2015.…”