Abstract:
:HIV-1 integrase (IN) is a retroviral enzyme that catalyses integration of the reverse-transcribed viral DNA into the host genome, which is necessary for efficient viral replication. In this study, we have performed an in silico virtual screening for the identification of potential HIV-1 IN strand transfer (ST) inhibitors. Pharmacophore modelling and atom-based 3D-QSAR studies were carried out for a series of compounds belonging to 3-Hydroxypyrimidine-2,4-diones. Based on the ligand-based pharmacophore model, we obtained a five-point pharmacophore with two hydrogen bond acceptors (A), one hydrogen bond donor (D), one hydrophobic group (H) and one aromatic ring (R) as pharmacophoric features. The pharmacophore hypothesis AADHR was used as a 3D query in a sequential virtual screening study to filter small molecule databases Maybridge, ChemBridge and Asinex. Hits matching with pharmacophore hypothesis AADHR were retrieved and passed progressively through Lipinski's rule of five filtering, molecular docking and hierarchical clustering. The five compounds with best hits with novel and diverse chemotypes were subjected to QM/MM docking, which showed improved docking accuracy. We further performed molecular dynamics simulation and found three compounds that form stable interactions with key residues. These compounds could be used as a leads for further drug development and rational design of HIV-1 IN inhibitors.
journal_name
SAR QSAR Environ Resjournal_title
SAR and QSAR in environmental researchauthors
Reddy KK,Singh SK,Tripathi SK,Selvaraj Cdoi
10.1080/1062936X.2013.772919subject
Has Abstractpub_date
2013-01-01 00:00:00pages
581-95issue
7eissn
1062-936Xissn
1029-046Xjournal_volume
24pub_type
杂志文章abstract::The Quantitative Ion Character-Activity Relationship (QICAR) method was used for correlating metal ionic characteristics with the maximum adsorption capacity (qmax) of multi-walled carbon for heavy metals. The experimental values of qmax for 25 heavy metal ions, estimated by the Langmuir isotherm model, were used to c...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2018.1538059
更新日期:2018-12-01 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::The Ames Salmonella typhimurium mutagenicity assay is a short-term bacterial reverse mutation test that was designed to detect mutagens. For several decades, it has been used in research laboratories and by regulatory agencies throughout the world for the detection and characterization of potential mutagens among natu...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2010.528959
更新日期:2010-10-01 00:00:00
abstract::The toxicological assessment of genotoxic impurities is important in the regulatory framework for pharmaceuticals. In this context, the application of promising computational methods (e.g. Quantitative Structure-Activity Relationships (QSARs), Structure-Activity Relationships (SARs) and/or expert systems) for the eval...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章,评审
doi:10.1080/1062936X.2012.657236
更新日期:2012-01-01 00:00:00
abstract::Genotoxicity is a key toxicity endpoint for current regulatory requirements regarding new and existing chemicals. However, genotoxicity testing is time-consuming and costly, and involves the use of laboratory animals. This has motivated the development of computational approaches, designed to predict genotoxicity with...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2013.820791
更新日期:2014-01-01 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::In Europe, agencies and official organizations involved in the pesticide control such as the EFSA, ECHA, JRC and ECETOC or even the OECD are pointing out that the software tools based on quantitative structure relationship models, i.e. QSAR and QSPR, have a huge potential to improve the pesticide risk assessment proce...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2019.1692368
更新日期:2020-01-01 00:00:00
abstract::Recent advances in the knowledge of parasite biology have unveiled many new antimalarial targets for drug development. The glycogen synthase kinase-3 from Plasmodium falciparum (PfGSK-3) plays an active role in the completion of the asexual erythrocytic stage of P. falciparum life cycle. Due to the limited availabilit...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2015.1104518
更新日期:2015-01-01 00:00:00
abstract::Density functional theory (DFT) at B3LYP/6-311G** level was employed to optimise the dioxin compounds, i.e., 25 polychlorinated or brominated dibenzo-p-dioxins (PCDDs or PBDDs) and 34 polychlorinated dibenzofurans (PCDFs) involved in this investigation. Three groups of descriptors mainly related to chemical reactivity...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360701428755
更新日期:2007-07-01 00:00:00
abstract::The human breast cancer resistance protein (BCRP), one of the members of the large ATP binding cassette (ABC) transporter superfamily, is crucial for resistance against chemotherapeutic agents. Currently, it has been emerged as one of the best biological targets for the designing of small molecule drugs capable of eli...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2020.1771769
更新日期:2020-06-01 00:00:00
abstract::Molecular similarity methods have emerged as powerful tools in analog selection, chemical classification based on toxic modes of action, and property estimation. The basic assumption of structure-activity relationships (SAR) is that similar structures usually have similar properties. Therefore, similarity methods can ...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360108035359
更新日期:2001-02-01 00:00:00
abstract::The relative toxicity (log IGC-1(50)) of 54 selected alkanones, both aliphatic and aromatic, as well as, alkenones and alkynones was evaluated in the static Tetrahymena pyriformis population growth assay. Excess toxicity, an indicator of bioreactivity, was associated only with the alpha-beta unsaturated alkenones and ...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629369508233991
更新日期:1995-01-01 00:00:00
abstract::QSAR models have been under development for decades but acceptance and utilization of model results have been slow, in part, because there is no widely accepted metric for assessing their reliability. We reapply a method commonly used in quantitative epidemiology and medical decision-making for evaluating the results ...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360290002280
更新日期:2002-03-01 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
abstract::The objective of this article is to outline both graph-theoretically based and quantum chemically based structural indices of potential use in quantitative structure activity correlations. We consider graph-theoretical indices such as the connectivity index, topological index, Wiener index and molecular ID indices. Se...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629369408028840
更新日期:1994-01-01 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::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::Aedes aegypti is the primary vector of several infectious viruses that cause yellow, dengue, chikungunya, and Zika fevers. Recently, plant-derived products have been tested as safe and eco-friendly larvicides against Ae. aegypti. The present study aimed to improve QSAR models for 62 larvicidal phytocompounds against A...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2020.1806922
更新日期:2020-10-01 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::An online resource has been developed for the theoretical study of hydration of biopolymers by the RISM (Reference Interaction Site Model) method, deriving from the integral equation theory of liquids. The online resource is based upon original software developed by the authors and includes all steps in studying a bio...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360802083707
更新日期:2008-04-01 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::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::Quantitative structure-activity relationship (QSAR) studies are useful computational tools often used in drug discovery research and in many scientific disciplines. In this study, a robust fragment-similarity-based QSAR (FS-QSAR) algorithm was developed to correlate structures with biological activities by integrating...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2011.569943
更新日期:2011-06-01 00:00:00
abstract::QSPR analyses of the solubility in water of 558 vapors, 786 liquids and 2045 solid organic neutral chemicals and drugs are presented. Simultaneous consideration of H-bond acceptor and donor factors leads to a good description of the solubility of vapors and liquids. A volume-related term was found to have an essential...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360412331319862
更新日期:2005-02-01 00:00:00
abstract::Quantitative structure-property relationship modelling can be a valuable alternative method to replace or reduce experimental testing. In particular, some endpoints such as octanol-water (KOW) and organic carbon-water (KOC) partition coefficients of polychlorinated biphenyls (PCBs) are easier to predict and various mo...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2016.1158734
更新日期:2016-04-01 00:00:00
abstract::On the basis of computer prediction of biological activity by PASS and toxicity by DEREK, the most prospective 18 alkylaminoacyl derivatives of 3-amino-benzo-[d]-isothiazole were selected. Their local anesthetic action was assessed using an in vitro preparation of the isolated peroneal nerve of the frog. The local ane...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629360310001624051
更新日期:2003-10-01 00:00:00
abstract::Knowledge of the interpolative region or applicability domain (AD) of structure-activity relationships is believed to improve predictive accuracy. The present work was undertaken to characterize the AD of EPI Suite biotransformation models and evaluate the performance of selected AD assessment methods. AD methods were...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2010.501816
更新日期:2010-07-01 00:00:00
abstract::The development of more efficient, ethical, and effective means of assessing the effects of chemicals on human health and the environment was a lifetime goal of Gilman Veith. His work has provided the foundation for the use of chemical structure for informing toxicological assessment by regulatory agencies the world o...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2014.907203
更新日期:2014-01-01 00:00:00
abstract::Thiobenzanilides are found to show strong biological activity as antimicrobial, antimycotic, and tuberculostatic agents. In addition, they are relatively weakly toxic to higher organisms. A large set of new (N-phenyl-)-2,4-dihydroxybenzenecarbothioamide derivatives was obtained. Preliminary studies showed high microbi...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/10629369908033221
更新日期:1999-12-01 00:00:00
abstract::γ-tubulin plays crucial role in the nucleation and organization of microtubules during cell division. Recent studies have also indicated its role in the regulation of microtubule dynamics at the plus end of the microtubules. Moreover, γ-tubulin has been found to be over-expressed in many cancer types, such as carcinom...
journal_title:SAR and QSAR in environmental research
pub_type: 杂志文章
doi:10.1080/1062936X.2015.1070200
更新日期:2015-06-01 00:00:00