A novel QSAR model for predicting induction of apoptosis by 4-aryl-4H-chromenes

Afantitis, Antreas; Melagraki, Georgia; Sarimveis, Haralambos; Koutentis, P. A.; Markopoulos, John; Igglessi‐Markopoulou, Olga

doi:10.1016/j.bmc.2006.05.061

Cited by 86 publications

(44 citation statements)

References 27 publications

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“…[55] The QSAR method has been described in detail in several publications. [56][57][58][59][60][61][62][63] Thus, we will give only brief summary. The QSAR approach has become a very useful tool in the prediction of the bioactivity of compounds.…”

Section: Resultsmentioning

confidence: 99%

Structure‐Activity Relationship Studies of a Number of α₁‐Adrenoceptor Antagonists and Antiarrhythmic Agents

Nowaczyk

Przybylski

Kulig

et al. 2010

Molecular Informatics

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Arylpiperazines represent one of the most studied classes of α1 -adrenoceptor (α1 -AR) antagonists. Currently, α1 -AR antagonists are useful in the treatment of benign prostatic hyperplasia, lower urinary tract symptoms or cardiac arrhythmia. The activity of various derivatives of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one as α1 -adrenergic receptor antagonists and antiarrhythmic (AA) agents was described using the qualitative inverse Structure Activity Relationship (SAR) model. The three-dimensional structures of the pyrrolidin-2-one derivatives in the basic form were obtained using AM1 semi-empirical quantum chemical calculations. All the molecules were geometry-optimized until the root-mean-square (RMS) gradient value was smaller than 10(-6) a.u. Single-point energy (SPE) calculations were performed at the DFT/B3LYP level of theory using the 6-31G** basis set. The main focus of this inverse SAR study is to find which features cause enhancing of antiarrhythmic properties between subtly different types of activity (α1 -adrenoreceptor antagonists and antiarrhythmic activities). Our SAR study involves the charge distribution in the plane of the pharmacophore model for α1 -AR. Suitable maps of the electrostatic potential were plotted based on the electronic and nuclear charge distribution obtained from the energy calculations. The results of this modelling study indicate that if the terminal arylpiperazine moiety is surrounded by regions of negative electrostatic potential, then the antiarrhythmic activity is blocked.

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Section: Resultsmentioning

confidence: 99%

Structure‐Activity Relationship Studies of a Number of α₁‐Adrenoceptor Antagonists and Antiarrhythmic Agents

Nowaczyk

Przybylski

Kulig

et al. 2010

Molecular Informatics

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“…Equation (5) The dataset was investigated for outliers, by calculating the standard residuals. Standardized residuals greater than 2 and less than À 2 are usually considered large [39]. Outliers should be removed in order to obtain the best statistical result [42].…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel CDK2 Inhibitors by QSAR and Virtual Screening Procedures

Babu

Smiles²,

Narasu

et al. 2008

QSAR Comb. Sci.

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Quantitative Structure -Activity Relationship (QSAR) studies were carried out on a set of 46 imidazo[1,2-a]pyridines, imidazo[1,2-b]pyridazines and 2,4-bis anilino pyrimidines, and nitroso-6-aminopyrimidine and 2,6-diaminopyrimidine inhibitors of CDK2 (Cyclin-dependent Kinase2) using a multiple regression procedure. The activity contributions of these compounds were determined from regression equation and the validation procedures such as external set cross-validation r 2 , (R 2 cv,ext ) and the regression of observed activities against predicted activities and vice versa for validation set were described to analyze the predictive ability of the QSAR model. An accurate and reliable QSAR model involving five descriptors was chosen based on the FIT Kubinyi function which defines the statistical quality of the model. The proposed model due to its high predictive ability was utilized to screen similar repertoire of compounds reported in the literature, and the biological activities are estimated. The screening study clearly demonstrated that the strategy presented shall be used as an alternative to the time-consuming experiments as the model tolerated a variety of structural modifications signifying its potential for drug design studies.

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“…13) Created models were validated using Leave-one-out cross-validation (LOO). 16,17) We consider a QSAR model predictive, if the following conditions are satisfied: R 2 >0.6 and Q 2 >0.5.…”

Section: Methodsmentioning

confidence: 99%

Statistical Analysis of the Impact of Molecular Descriptors on Cytotoxicity of Thiourea Derivatives Incorporating 2-Aminothiazole Scaffold

et al. 2016

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Chemical reactivity descriptors and lipophilicyty (log P) were evaluated via semi-empirical method for the quantum calculation of molecular electronic structure (PM3) in order to clarify the structure-cytotoxic activity relationships of disubstutited thioureas. Analysed compounds were obtained by the linkage of 2-aminothiazole ring, thiourea and substituted phenyl ring. The detailed examination was carried out to establish correlation between descriptors and cytotoxic activity against the MT-4 cells for 11 compounds. For the most active compounds (6 compounds) cytotoxic activity against three cancer cell lines (CCRF-CEM, WIL-2NS, CCRF-SB) and normal human cell (HaCaT) was determined. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release were assessed. Regression analysis revealed that electrophilicity index and chemical potential significantly contributed to expain the thioureas cytotoxic potential.

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A novel QSAR model for predicting induction of apoptosis by 4-aryl-4H-chromenes

Cited by 86 publications

References 27 publications

Structure‐Activity Relationship Studies of a Number of α₁‐Adrenoceptor Antagonists and Antiarrhythmic Agents

Structure‐Activity Relationship Studies of a Number of α₁‐Adrenoceptor Antagonists and Antiarrhythmic Agents

Identification of Novel CDK2 Inhibitors by QSAR and Virtual Screening Procedures

Statistical Analysis of the Impact of Molecular Descriptors on Cytotoxicity of Thiourea Derivatives Incorporating 2-Aminothiazole Scaffold

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A novel QSAR model for predicting induction of apoptosis by 4-aryl-4H-chromenes

Cited by 86 publications

References 27 publications

Structure‐Activity Relationship Studies of a Number of α1‐Adrenoceptor Antagonists and Antiarrhythmic Agents

Structure‐Activity Relationship Studies of a Number of α1‐Adrenoceptor Antagonists and Antiarrhythmic Agents

Identification of Novel CDK2 Inhibitors by QSAR and Virtual Screening Procedures

Statistical Analysis of the Impact of Molecular Descriptors on Cytotoxicity of Thiourea Derivatives Incorporating 2-Aminothiazole Scaffold

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Product

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Structure‐Activity Relationship Studies of a Number of α₁‐Adrenoceptor Antagonists and Antiarrhythmic Agents

Structure‐Activity Relationship Studies of a Number of α₁‐Adrenoceptor Antagonists and Antiarrhythmic Agents