Abstract:
:Drug discovery and development research is undergoing a paradigm shift from a linear and sequential nature of the various steps involved in the drug discovery process of the past to the more parallel approach of the present, due to a lack of sufficient correlation between activities estimated by in vitro and in vivo assays. This is attributed to the non-drug-likeness of the lead molecules, which has often been detected at advanced drug development stages. Thus a striking aspect of this paradigm shift has been early/parallel in silico prioritization of drug-like molecular databases (also database pre-processing), in addition to prioritizing compounds with high affinity and selectivity for a protein target. In view of this, a drug-like database useful for virtual screening has been created by prioritizing molecules from 36 catalog suppliers, using our recently derived binary QSAR based drug-likeness model as a filter. The performance of this model was assessed by a comparative evaluation with respect to commonly used filters implemented by the ZINC database. Since the model was derived considering all the limitations that have plagued the existing rules and models, it performs better than the existing filters and thus the molecules prioritized by this filter represent a better subset of drug-like compounds. The application of this model on exhaustive subsets of 4,972,123 molecules, many of which have passed the ZINC database filters for drug-likeness, led to a further prioritization of 2,920,551 drug-like molecules. This database may have a great potential for in silico virtual screening for discovering molecules, which may survive the later stages of the drug development research.
journal_name
SAR QSAR Environ Resjournal_title
SAR and QSAR in environmental researchauthors
Saxena AK,Prathipati Pdoi
10.1080/10629360600884462subject
Has Abstractpub_date
2006-08-01 00:00:00pages
371-92issue
4eissn
1062-936Xissn
1029-046Xpii
MK8K36P6442026P6journal_volume
17pub_type
杂志文章abstract::Retrometabolic drug design approaches incorporate metabolic and toxicological considerations into the drug design process and represent a novel, systematic methodology for the design of safe compounds. Two major design concepts aimed to increase the therapeutic index (the activity/toxicity ratio) of drugs were develop...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章,评审
doi:10.1080/10629369808033261
更新日期:1998-01-01 00:00:00
abstract::The aim of this study was to evaluate a multivariate statistical model, utilising Partial Least Squares (PLS) analysis, for the prediction of the acute toxicity of aliphatic chemicals to the ciliate Tetrahymena pyriformis. A model was developed that was capable of making a prediction regardless the mechanism of toxic ...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936032000101501
更新日期:2003-08-01 00:00:00
abstract::Artificial neural networks (ANN) can be used for the direct QSAR analysis of percent effect biological data, thus avoiding the bias introduced by arbitrarily chosen classes and the loss of information due to prior classification. For two data sets the ANN results are compared with those obtained by adaptive least squa...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629369308028825
更新日期:1993-01-01 00:00:00
abstract::Three modelling systems (MultiCase®, LeadScope® and MDL® QSAR) were used for construction of androgenic receptor antagonist models. There were 923-942 chemicals in the training sets. The models were cross-validated (leave-groups-out) with concordances of 77-81%, specificity of 78-91% and sensitivity of 51-76%. The spe...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2010.528981
更新日期:2011-03-01 00:00:00
abstract::The relative toxicity (log IGC50(-1)) of 49 selected aliphatic amines and aminoalkanols was evaluated in the static Tetrahymena pyriformis population growth impairment assay. Excess toxicity, indicated by potency greater than predicted for non-polar narcotic alkanols, was associated with both classes of test chemicals...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629369808039157
更新日期:1998-01-01 00:00:00
abstract::Perfluorinated chemicals (PFCs) form a special category of organofluorine compounds with particularly useful and unique properties. Their large use over the past decades increased the interest in the study of their environmental fate. Fluorocarbons may have direct or indirect environmental impact through the products ...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936032000169688
更新日期:2004-02-01 00:00:00
abstract::Three-dimensional quantitative structure-activity relationship (3D-QSAR) modelling was conducted on a series of leucine-rich repeat kinase 2 (LRRK2) antagonists using CoMFA and CoMSIA methods. The data set, which consisted of 37 molecules, was divided into training and test subsets by using a hierarchical clustering m...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2016.1184713
更新日期:2016-05-01 00:00:00
abstract::The Index of Ideality of Correlation (IIC) is a new criterion of the predictive potential for quantitative structure-property/activity relationships. The value of the IIC is a mathematical function sensitive to the value of the correlation coefficient and dispersion (expressed via mean absolute error). The IIC has bee...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2019.1615547
更新日期:2019-06-01 00:00:00
abstract::Quantitative structure-property relationship (QSPR) models were developed for predicting the pungency of a set of capsaicinoids. Multiple linear regression (MLR) coupled with topological substructural molecular descriptor (TOPS-MODE) approach was used. The best MLR model based on only five orthogonalized TOPS-MODE var...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2020.1777583
更新日期:2020-07-01 00:00:00
abstract::A special challenge in the new European Union chemicals legislation, Registration, Evaluation and Authorisation of Chemicals, will be the toxicological evaluation of chemicals for reproductive toxicity. Use of valid quantitative structure-activity relationships (QSARs) is a possibility under the new legislation. This ...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360802550473
更新日期:2008-01-01 00:00:00
abstract::Modern industrialisation has led to the production of millions of toxic chemicals having hazardous effects on the ecosystem. It is impracticable to determine the toxic potential of a large number of chemicals in animal models, making the use of quantitative structure-toxicity relationship (QSTR) models an alternative ...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2011.645872
更新日期:2012-01-01 00:00:00
abstract::Molecular modelling studies were performed to identify the essential structural requirements of quinoline-based derivatives for improving their antimalarial activity. The developed CoMFA, CoMSIA and HQSAR models for a training set comprising 37 derivatives showed good statistical significance in terms of internal cros...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2013.875484
更新日期:2014-01-01 00:00:00
abstract::Neurotoxicities of a series of solvents in rats and mice have been modeled by means of the TOPS-MODE approach. Two quantitative structure-toxicity relationship (QSTR) models were obtained explaining more than 80% of the variance in the experimental values of neurotoxicity of 45 solvents. Only one compound was detected...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360108035384
更新日期:2001-01-01 00:00:00
abstract::To develop quantitative structure-activity relationships (QSAR) models capable of predicting adverse effects for large chemical inventories and diverse structures, an interactive approach is presented that includes testing of strategically selected chemicals to expand the scope of a preliminary model to cover a target...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360902723996
更新日期:2009-01-01 00:00:00
abstract::Semiempirical quantum calculations were performed on a series of organophosphorus fluoridates to determine the relative reactivity for hydrolysis. This value was determined by subtracting the energy of the metastable intermediate from the energy of the stable molecule. Plotting this relative reactivity for each compou...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629369908039176
更新日期:1999-01-01 00:00:00
abstract::A quantitative structure-activity relationship (QSAR) study on 43 amide repellents was carried out by the heuristic method in order to reveal the correlations between molecular parameters of these amides and their repellency against Aedes aegypti. Sketches and optimizations of molecular structures were achieved by the...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2017.1320585
更新日期:2017-04-01 00:00:00
abstract::The present theoretical study analyses the Quantum QSPR fundamental linear equation predictive power. Two main alternative algorithms, among several possible choices, are fully described in an add one and add many basis, while the other possibilities are only sketched out. It is shown that one can also apply the descr...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360701304113
更新日期:2007-05-01 00:00:00
abstract::The hydrogen bonding interaction between pyridine bases and water was theoretically studied by applying density functional theory computations at the B3LYP/631G(d,p) level. The theoretically determined binding energies for the complexation process correlate well with the experimental solvatochromic parameters beta for...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360410001724914
更新日期:2004-08-01 00:00:00
abstract::The evaluation of persistency of chemicals in environmental media (water, soil, sediment) is included in European Regulations, in the context of the Persistence, Bioaccumulation and Toxicity (PBT) assessment. In silico predictions are valuable alternatives for compounds screening and prioritization. However, already e...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2020.1776387
更新日期:2020-07-01 00:00:00
abstract::Matrix metalloproteinase-2 (MMP-2) is a potential target in anticancer drug discovery due to its association with angiogenesis, metastasis and tumour progression. In this study, 67 glutamic acid derivatives, synthesized and evaluated as MMP-2 inhibitors, were taken into account for multi-QSAR modelling study (regressi...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2017.1406986
更新日期:2018-01-01 00:00:00
abstract::Aldehydes are toxic environmental contaminants which cause severe health hazards. There is a growing need by industries and regulatory agencies for the development of tools able to assess the potential hazardous effects of chemicals on living organisms. In this background, multivariate image analysis combined with qua...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2013.840678
更新日期:2013-01-01 00:00:00
abstract::Biofouling in the marine environment is a major problem. In this study, three marine organisms, namely Bacillus flexus (LD1), Pseudomonas fluorescens (MD3) and Vibrio natriegens (MD6), were isolated from biofilms formed on polymer and metal surfaces immersed in ocean water. Phylogenetic analysis of these three organis...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629361003771009
更新日期:2010-04-01 00:00:00
abstract::Chagas disease is endemic to 21 Latin American countries and is a great public health problem in that region. Current chemotherapy remains unsatisfactory; consequently the need to search for new drugs persists. Here we present a new approach to identify novel compounds with potential anti-chagasic action. A large data...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2020.1863857
更新日期:2021-01-01 00:00:00
abstract::A series of diphenyl ether derivatives were developed and showed promising potency for inhibiting InhA, an essential enoyl acyl carrier protein reductase involved in mycolic acid biosynthesis, leading to the lysis of Mycobacterium tuberculosis. To understand the structural basis of diphenyl ether derivatives for desig...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2014.898690
更新日期:2014-01-01 00:00:00
abstract::Literature data on the toxicity of chlorophenols for three luminescent bacteria (Vibrio fischeri, and the lux-marked Pseudomonas fluorescens 10586s pUCD607 and Burkholderia spp. RASC c2 (Tn4431)) have been analyzed in relation to a set of computed molecular physico-chemical properties. The quantitative structure-toxic...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629369908039112
更新日期:1999-01-01 00:00:00
abstract::This article represents a minireview of work published so far in the 21st century in the in silico ADMET field of research related to investigations in the areas of solubility, hERG and cytochrome P450 3A4. Various approaches including 2D- and 3D-QSARs and pharmacophore modelling are discussed. The pros and cons of th...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章,评审
doi:10.1080/10629360412331319835
更新日期:2005-02-01 00:00:00
abstract::As often noted by Dr. Gilman Veith, a major barrier to advancing any model is defining its applicability domain. Sulfur-containing industrial organic chemicals can be grouped into several chemical classes including mercaptans (RSH), sulfides (RSR'), disulfides (RSSR'), sulfoxides (RS(=O)R'), sulfones (RS(=O)(=O)R'), s...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2014.898693
更新日期:2014-01-01 00:00:00
abstract::Topological structure methods are used to model fish toxicity against three classes of organic chemicals. The models were obtained independent of 3D structure information. Further, no mechanism of partitioning was assumed, thus avoiding the problems associated with selection of partitioning system for computation of l...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936031000073144
更新日期:2003-04-01 00:00:00
abstract::Chemical structures of organic compounds are characterized numerically by a variety of structural descriptors, one of the earliest and most widely used being the Wiener index W, derived from the interatomic distances in a molecular graph. Extensive use of distance-based structural descriptors or topological indices ha...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360108035368
更新日期:2001-01-01 00:00:00
abstract::Peroxysome proliferator-activated receptors (PPARs) have grown greatly in importance due to their role in the metabolic profile. Among three subtypes (α, γ and δ), we here consider the least investigated δ subtype to explore the molecular fingerprints of selective PPARδ agonists. Validated QSAR models (regression base...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2015.1039576
更新日期:2015-01-01 00:00:00