Insolubility is a crucial issue in drug design because insoluble compounds are often measured to be inactive although they might be active if they were soluble. We provide and analyze various insolubility classification models based on a recently published data set and compounds measured in-house at Boehringer-Ingelheim. The 2D descriptor ...

Log P(OW), the negative logarithm of the octanol-water partition coefficient, is omnipresent in computational drug design. Here, we present a surface-integral model for calculating log P(OW). The model is based on local properties calculated using AM1 semiempirical molecular orbital theory. These are the molecular electrostatic potential (MEP), local ionization energy ...

Many articles in "in silico" drug design implemented genetic algorithm (GA) for feature selection, model optimization, conformational search, or docking studies. Some of these articles described GA applications to quantitative structure-activity relationships (QSAR) modeling in combination with regression and/or classification techniques. We reviewed the implementation of GA in drug design ...

A quantitative structure-property relationship (QSPR) study was performed for the prediction of the absorption maxima (lambda(max)) of organic dyes for dye-sensitized solar cells (DSSCs). The entire set of 70 dyes was divided into a training set of 53 dyes and a test set of 17 dyes according to Kennard and ...

A quantitative structure property relationship (QSPR) study was performed to develop a model for prediction of flash point of esters based on a diverse set of 95 components. The most five important descriptors were selected from a set of 1124 descriptors to build the QSPR model by means of a ...

Based on the local Shannon entropy concept in information theory, a new measure of aromaticity is introduced. This index, which describes the probability of electronic charge distribution between atoms in a given ring, is called Shannon aromaticity (SA). Using B3LYP method and different basis sets (6-31G**, 6-31+G** and 6-311++G**), the ...

The development of a new quantitative structure-property relationship (QSPR) model to predict aqueous solubility (S(w)) accurately for compounds of military interest is presented. The ability of the new model to predict solubility is assessed and compared to available experimental data. A large set of structurally diverse organic compounds was used ...

Quantitative structure-activity relationship study on three diverse sets of structurally similar fluoroquinolones was performed using a comprehensive set of molecular descriptors. Multiple linear regression technique was applied as a preprocessing tool to find the set of relevant descriptors (10) which are subsequently used in the artificial neural networks approach (non-linear ...

Aldose Reductase (AR), the key enzyme of the polyol pathway catalyzes the reduction of glucose to sorbitol using nicotinamide adenine dinucleotide phosphate as an essential cofactor, has been demonstrated to play an important role in the pathogenesis of diabetic complications. Self Organizing Molecular Field Analysis (SOMFA), a novel three-dimensional quantitative ...

A linear quantitative structure activity relationship (QSAR) model is presented for modeling and predicting the inhibition of HIV-1 integrase. The model was produced by using the stepwise multiple linear regression technique on a database that consists of 67 recently discovered 1,3,4-oxadiazole substituted naphthyridine derivatives. The developed QSAR model was evaluated ...

A structurally diverse dataset of 119 compounds was used to develop and validate a 2D binary QSAR model for the LPA(3) receptor. The binary QSAR model was generated using an activity threshold of greater than 15% inhibition at 10 microM. The overall accuracy of the model on the training set ...

In this work we developed a 3D-pharmacophore model for sigma(2) receptor based on 19 benzooxazolone derivatives. The best 3D-pharmacophore hypothesis, consisting of five features: a positive ionizable, a hydrogen bond acceptor, a hydrophobic aromatic, a hydrophobic aliphatic, and a generic hydrophobic provided a 3D-QSAR model with a correlation coefficient of ...

Aromatase (cytochrome 19) inhibitors have emerged as promising candidates for treatment of breast cancer. In search of potent aromatase inhibitors, docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using molecular shape, spatial, electronic, structural and thermodynamic descriptors have been performed on a diverse set of compounds having human aromatase inhibitory ...

CCR5 is the key receptor of HIV-1 virus entry into host cells and it becomes an attractive target for antiretroviral drug design. To date, six types of CCR5 antagonist were synthesized and evaluated. To search more potent bio-active compounds, non-linear support vector machine was used to construct the relationship models ...

Predictive pharmacophore models have been developed for a series of arylamino-substituted benzo[b]thiophenes exhibiting free radical scavenging activity. 3D pharmacophore models were generated using a set of 20 training set compounds and subsequently validated by mapping 6 test set compounds using Discovery Studio 2.1 software. Further model validation was performed by ...

Chagas disease is nowadays the most serious parasitic health problem. This disease is caused by Trypanosoma cruzi. The great number of deaths and the insufficient effectiveness of drugs against this parasite have alarmed the scientific community worldwide. In an attempt to overcome this problem, a model for the design and ...

QSAR analyses were performed on a series of trans-stilbenoid diaryl compounds for modeling their COX-2 inhibitory activities. The multivariate regression equations were developed with the selected independent variables using various feature selection methods. In addition, model training was done using different test-train data selection methods. The applicability of each variable ...

In this paper, we describe an in silico first principal approach to predict the mutagenic potential of primary aromatic amines. This approach is based on the so-called "nitrenium hypothesis", which was developed by Ford et al. in the early 1990s. This hypothesis asserts that the mutagenic effect for this class ...

Quantitative structure-activity relationship (QSAR) methods aim to build quantitatively predictive models for the discovery of new molecules. It has been widely used in medicinal chemistry for drug discovery. Many QSAR techniques have been developed since Hansch's seminal work, and more are still being developed. Motivated by Hopfinger's receptor-dependent QSAR (RD-QSAR) ...

Thiazolidinediones (TZDs) have been recently developed to treat diabetic patients that can reverse insulin resistance by activation of gamma isoform of peroxisome proliferator-activated receptor (PPAR-gamma). Self-Organizing Molecular Field Analysis (SOMFA) has been performed on TZD scaffold having h-PTP1B inhibitory activities for the development and optimization of lead. The master grids ...

A combined application of statistical molecular design (SMD), quantitative structure-activity relationship (QSAR) modeling and prediction of new active compounds was effectively used to develop salicylidene acylhydrazides as inhibitors of type III secretion (T3S) in the Gram-negative pathogen Yersinia pseudotuberculosis. SMD and subsequent synthesis furnished 50 salicylidene acylhydrazides in high purity. ...

The informatics on benzenoid hydrocarbons and related systems is reviewed. This informatics involves a collection of algorithms used to discover, process, and analyze patterns in structure/formula data sets. The unique organizational structure that emerges will be useful to chemists with an interest in polycyclic aromatic compounds, environmental chemists, material scientists, ...

Chromatographic retention data obtained from interactions between some oxime-type compounds and different stationary phases (involving hydrophobic interaction, ion pairing formation availability, pi-pi, H-bonding, dipole-dipole, ion-dipole, electrostatic interaction and glycoprotein binding ability) have been studied. The logarithms of the capacity factors extrapolated at 0% or 100% organic solvent, resulting from the ...

The search for molecules with activity against Mycobacterium tuberculosis (Mtb) is employing many approaches in parallel including high throughput screening and computational methods. We have developed a database (CDD TB) to capture public and private Mtb data while enabling data mining and collaborations with other researchers. We have used the ...

OBJECTIVE: The purpose of this study is to develop a quantitative structure-activity relationship (QSAR) model that can distinguish mutagenic from non-mutagenic species with alpha,beta-unsaturated carbonyl moiety using two endpoints for this activity - Ames test and mammalian cell gene mutation test - and also to gather information about the molecular ...

Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can simulate biopartioning process of many kinds of drugs and describe their biological behavior. The capability of BMC to describe and estimate pharmacokinetic and pharmacodynamic parameters of ...

BACKGROUND: A statistical model, built using the CODESSA software package, was developed to describe the relationship between the structure of nostoclide derivatives and their ability to interfere with the electron transport chain in the Hill reaction. RESULTS: A QSAR treatment was carried out on a series of compounds designed using ...

A chemical feature-based pharmacophore model was developed for Tumor Necrosis Factor-alpha converting enzyme (TACE) inhibitors. A five point pharmacophore model having two hydrogen bond acceptors (A), one hydrogen bond donor (D) and two aromatic rings (R) with discrete geometries as pharmacophoric features was developed. The pharmacophore model so generated was ...

Tuberculosis (TB) is the primary cause of mortality among infectious diseases. Mycobacterium tuberculosis monophosphate kinase (TMPKmt) is essential to DNA replication. Thus, this enzyme represents a promising target for developing new drugs against TB. In the present study, the receptor-independent, RI, 4D-QSAR method has been used to develop QSAR models ...

Carbamates are a well-established class of fatty acid amide hydrolase (FAAH) inhibitors. Here we describe the synthesis of meta-substituted phenolic N-alkyl/aryl carbamates and their in vitro FAAH inhibitory activities. The most potent compound, 3-(oxazol-2yl)phenyl cyclohexylcarbamate (2 a), inhibited FAAH with a sub-nanomolar IC(50) value (IC(50)=0.74 nM). Additionally, we developed and ...

Phosphoinositide 3-kinases (PI3Ks) inhibitors have treatment potential for cancer, diabetes, cardiovascular disease, chronic inflammation and asthma. A consensus model consisting of three base classifiers (AODE, kNN, and SVM) trained with 1,283 positive compounds (PI3K inhibitors), 16 negative compounds (PI3K non-inhibitors) and 64,078 generated putative negatives was developed for predicting compounds ...

Tuberculosis is an infection caused mainly by Mycobacterium tuberculosis. A first-line antimycobacterial drug is pyrazinamide (PZA), which acts partially as a prodrug activated by a pyrazinamidase releasing the active agent, pyrazinoic acid (POA). As pyrazinoic acid presents some difficulty to cross the mycobacterial cell wall, and also the pyrazinamide-resistant strains ...

Cathepsin B is a potential target for the development of drugs to treat several important human diseases. A number of inhibitors targeting this protein have been developed in the past several years. Recently, a group of small molecules were identified to have inhibitory activity against cathepsin B through high throughput ...

Quantitative structure-activity relationships (QSAR) for prediction of binding affinities (pEC50, i.e., minus decimal logarithm of the 50% effective concentration) of 20 fullerene derivatives inhibitors of the HIV-1 PR (human immunodeficiency virus type 1 protease) have been developed by application of the optimal descriptors approach calculated with SMILES (simplified molecular input ...

In this work a quantitative structure-activity relationship (QSAR) technique was developed to investigate the air to liver partition coefficient (log Kliver) for volatile organic compounds (VOCs). Suitable set of molecular descriptors was calculated and the important descriptors were selected by GA-PLS methods. These variables were served as inputs to generate ...

A series of human immunodeficiency virus type 1 (HIV-1) attachment inhibitors were subjected to ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. The CoMFA model yielded satisfactory statistical data with the cross-validated q2 value of 0.589 ...

A new strategy for biomarker discovery is presented that uses time-series metabolomics data. Data sets from samples analysed at different time points after an intervention are searched for compounds that show a meaningful trend following the intervention. Obviously, this requires new data-analytical tools to distinguish such compounds from those showing ...

A COSMO-RS descriptor (S(sigma-profile)) has been used in quantitative structure-property relationship (QSPR) studies by a neural network (NN) for the prediction of empirical solvent polarity E(T)(N) scale of neat ionic liquids (ILs) and their mixtures with organic solvents. S(sigma-profile) is a two-dimensional quantum chemical parameter which quantifies the polar electronic ...

The experimental logEC50 toxicity values of 104 compounds causing bioluminescent repression of the bacterium strain Pseudomonas isolated from an industrial wastewater were studied. Using the Best Multilinear Regression method implemented in CODESSA PRO, models with up to 8 theoretical descriptors were obtained. Utilizing a rigorous descriptor selection and validation procedure ...

We present a process model that predicts the removal of the antibiotic micropollutants, sulfamethoxazole (SMX), tetracycline (TCY), and ciprofloxacin (CIP), in an activated sludge treatment system. A novel method was developed to solve the inverse problem of inferring process rate, sorption, and correction factor parameter values from batch experimental results ...

We performed a predictive analysis based on Quantitative Structure-Activity Relationships (QSAR) of a very important property of flavonoids which is the inhibition (IC50) of influenza H1N1 virus neuraminidase. The best linear model constructed from 20 molecular structures incorporated four molecular descriptors, selected from more than a thousand geometrical, topological, quantum-mechanical ...

Computational chemistry is playing an increasingly important role in drug design and discovery, structural biology, and quantitative structure-activity relationship (QSAR) studies. For QSAR work, selecting an appropriate and accurate method to assign the electrostatic potentials of each atom in a molecule is a critical first step. So far several commonly ...

Three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking studies were carried out to explore the binding of 73 inhibitors to dipeptidyl peptidase IV (DPP-IV), and to construct highly predictive 3D-QSAR models using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The negative logarithm of IC(50) (pIC(50)) ...

The Parallel Artificial Membrane Permeability Assay (PAMPA) has been successfully introduced into the pharmaceutical industry to allow useful predictions of passive oral absorption. Over the last 5 years, researchers have modified the PAMPA such that it can also evaluate passive blood-brain barrier (BBB) permeability. This paper compares the permeability of ...

The International Chemical Identifier (InChI) has been used to construct InChI-based optimal descriptors to model the binding affinity for fullerene[C60]-based inhibitors of human immunodeficiency virus type 1 aspartic protease (HIV-1 PR). Statistical characteristics of the one-variable model obtained by the balance of correlations are as follows: n=8, r(2)=0.9769, q(2)(LOO)=0.9646, s=0.099, ...

We report the development of CoMFA analysis models that correlate the 3D chemical structures of 80 compounds with 6-5 fused ring system synthesized in our laboratory and their inhibitory potencies against tgDHFR and rlDHFR. In addition to conventional CoMFA analysis, we used two routines available in the literature aimed at ...

The quantitative structure-property relationship (QSPR) methodology was applied to predict the decomposition enthalpies of 22 nitroaromatic compounds, used as indicators of thermal stability. An extended series of descriptors (constitutional, topological, geometrical charge related and quantum chemical) was calculated at two different levels of theory: density functional theory (DFT) and semi-empirical ...

The activities of a series of HIV reverse transcriptase inhibitor TIBO derivatives were recently modeled by using genetic function approximation (GFA) and artificial neural networks (ANN) on topological, structural, electronic, spatial and physicochemical descriptors. The prediction results were found to be superior to those previously established. In the present work, ...

The highly potent and kappa-opioid (KOP) receptor-selective hallucinogen Salvinorin A and selected analogs have been analyzed using the 3D quantitative structure-affinity relationship technique Comparative Molecular Field Analysis (CoMFA) in an effort to derive a statistically significant and predictive model of salvinorin affinity at the KOP receptor and to provide additional ...

Furanocoumarin derivatives (FCs) present in grapefruit and other plants cause pharmacokinetic interactions such as increased absorption of various drugs because the constituents have inhibitory effects on drug metabolizing activities of cytochrome P450 (CYP) 3A that is expressed in intestinal mucosal cells. Though it has been 20 years since such an ...