Abstract:
:The apparently paradoxical lack of correlation between the huge increase in the discovery of new potential drug targets made possible by the post-genomic sciences and new drugs development has stimulated many different interpretations. Here we illustrate the general principle of redundancy of biological pathways on hand of simplified mathematical approaches applied to different models of biological regulation. The simulation was based on the analysis of the 'degree of autonomy' of network architectures in which the possibility for an external stimulus (e.g. a drug) impinging into a specific node to be sensed by the entire network, and eventually amplified up to a macroscopic consequence, was demonstrated to be limited to strictly linear pathways. The implications of such a result for poly-pharmacology and computational approaches to drug development are described as well.
journal_name
Curr Comput Aided Drug Desjournal_title
Current computer-aided drug designauthors
Tun K,Menghini M,D'Andrea L,Dhar P,Tanaka H,Giuliani Adoi
10.2174/157340911796504297subject
Has Abstractpub_date
2011-09-01 00:00:00pages
206-13issue
3eissn
1573-4099issn
1875-6697pii
BSP/CCADD/E-Pub/000031ajournal_volume
7pub_type
杂志文章abstract::Pakistan possesses a rich and vast source of natural products (NPs). Some of these secondary metabolites have been identified as potent therapeutic agents. However, the medicinal usage of most of these compounds has not yet been fully explored. The discoveries for new scaffolds of NPs as inhibitors of certain enzymes ...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/157340991102150904101740
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Chemotherapy and radiotherapy have negative effects on normal tissues and they are very expensive and lengthy treatments. These disadvantages have recently attracted researchers to the new methods that specifically affect cancerous tissues and have lower damage to normal tissues. One of these methods is the ...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409914666181012151242
更新日期:2020-01-01 00:00:00
abstract::An important area of theoretical drug design research is quantitative structure activity relationship (QSAR) using structural invariants. The impetus for this research trend comes from various directions. Researchers in chemical documentation have searched for a set of invariants which will be more convenient than the...
journal_title:Current computer-aided drug design
pub_type: 杂志文章,评审
doi:10.2174/157340912800492384
更新日期:2012-06-01 00:00:00
abstract::A 3D-QSAR selectivity analysis of 53 adamantyl heteroaryl urea derivatives active against M. tuberculosis is reported. These analogs inhibit Mycobacterial Membrane Protein Large 3 (MmpL3), a proposed transporter for cell wall mycolic acids. However, these analogs also exhibit affinity towards human soluble epoxide hyd...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409911666150803154114
更新日期:2015-01-01 00:00:00
abstract::3D pharmacophore modeling is an important computational methodology for ligand-enzyme binding interactions in drug discovery. More specifically, a consensus pharmacophore model derived from diverse ligands is a key determinant upon which the prediction power of computational models is based for designing novel ligands...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/157340912803519615
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Thiadiazole not only acts as "hydrogen binding domain" and "two-electron donor system" but also as constrained pharmacophore. METHODS:The maleate salt of 2-((2-hydroxy-3-((4-morpholino-1, 2,5-thiadiazol-3-yl) oxy) propyl) amino)- 2-methylpropan-1-ol (TML-Hydroxy)(4) has been synthesized. This methodology in...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409915666190206142756
更新日期:2019-01-01 00:00:00
abstract::Chemical and molecular graphs have fundamental applications in chemoinformatics, quantitative structureproperty relationships (QSPR), quantitative structure-activity relationships (QSAR), virtual screening of chemical libraries, and computational drug design. Chemoinformatics applications of graphs include chemical st...
journal_title:Current computer-aided drug design
pub_type: 杂志文章,评审
doi:10.2174/1573409911309020002
更新日期:2013-06-01 00:00:00
abstract::Recent studies have demonstrated several biological activities of curcumin with therapeutic potential against Alzheimer's disease, among them the inhibition of the enzyme acetylcholinesterase (AChE). Aiming at identifying the chemical features relevant for this activity, the inhibition of curcumin and a set of 7 deriv...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/15734099113099990007
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Secreted Frizzled-Related Protein 4 (SFRP4) is a glycoprotein that acts as a competitor of both canonical and non-canonical Wnt pathways. SFRP4 is mostly expressed in ovary and plays a significant role as a target molecule to cure ovarian carcinoma. OBJECTIVE:Multiple chemical agonists are being used to cur...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409914666180112100122
更新日期:2018-01-01 00:00:00
abstract::As crucial members of the G-protein coupled receptor (GPCR) superfamily, alpha (1)-adrenergic receptors (alpha(1)-ARs) are recognized to intervene the actions of endogenous catecholamines such as norepinephrine and epinephrine. So far three distinct alpha(1)-AR subtypes, alpha(1A), alpha(1B) and alpha(1D), have been c...
journal_title:Current computer-aided drug design
pub_type: 杂志文章,评审
doi:10.2174/157340910791760082
更新日期:2010-09-01 00:00:00
abstract:AIM AND OBJECTIVE:Isoflavone phytoestrogens, which commonly present in natural plants, are closely related to human health. The combination of them with estrogen receptors in the body can play a more important role in the prevention and treatment of cardiovascular diseases, cancer, and menopausal diseases. This researc...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409916666200712140245
更新日期:2020-07-12 00:00:00
abstract::Hepatocellular Carcinoma is the most common primary malignant tumor of the liver. Development of multidrug resistance is the main obstacle to the success of anticancer drugs. In this study, designing and docking study of thiosemicarbazide hybrids with amino acids or peptides against hepatocellular carcinoma was perfor...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409911666151103114300
更新日期:2015-01-01 00:00:00
abstract::The paper is an attempt for QSAR modeling based on topological, electrostatic, quantum chemical, constitutional, geometrical and physicochemical indices computed from the structures of 59 set of synthesized chalcone derivatives tested for the cell cycle inhibition of mitotic G2/M phase using multiple linear regression...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409911666150702101559
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Various applications of nanosubstances in industrial and consumer goods sectors are growing rapidly because of their useful chemical and physical properties. OBJECTIVES:Assessment of hazard posed by exposure to nanosubstances is essential for the protection of human and ecological health. METHODS:We analyz...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409912666160824145722
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Identification and development of new drug candidates to be used singly or in combination therapy is critical in anticancer research. In recent years, accumulating evidence encouraged us to investigate the anti-proliferative effects of a small and emerging phytochemical Wedelolactone (WDL) in estrogen-depend...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409915666191015113134
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Euterpe oleracea Martius, popularly known as açaí, is a fruit rich in α-tocopherols, fibers, lipids, mineral ions and polyphenols. It is believed that the high content of polyphenols, specially flavonoids, provides several health-promoting effects to the açaí fruit, including anti-inflammatory, immunomodulat...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409916666200619122803
更新日期:2020-06-19 00:00:00
abstract::For three random splits, one-variable models of oximes reactivation of sarin inhibited acetylcholinesterase (logarithm of the AChE reactivation percentage by oximes with concentration of 0.001 M) have been calculated with CORAL software. The total number of considered oximes was 42. Simplified molecular input line ent...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:
更新日期:2014-11-26 00:00:00
abstract:BACKGROUND:Trypanosoma brucei (T. brucei) is the cause of the deadly human African trypanosomiasis (HAT) with a case fatality ratio of 10%. OBJECTIVE:Targeting the essential Trypanosomal glucose metabolism pathway through the inhibition of phosphoglycerate kinase (PGK) and glyceraldehyde-3-phosphate dehydrogenase (GAP...
journal_title:Current computer-aided drug design
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doi:10.2174/1573409916666200722140704
更新日期:2020-07-22 00:00:00
abstract:BACKGROUND:Mixed ligand-metal complexes are efficient chelating agents because of flexible donor ability. Mixed ligand complexes containing hetero atoms sulphur, nitrogen and oxygen have been probed for their biological significance. OBJECTIVE:Nine mixed ligand-metal complexes of 2-(butan-2-ylidene) hydrazinecarbothio...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409915666190926122103
更新日期:2019-09-26 00:00:00
abstract::Interrelated Two-way Clustering (ITC) is an unsupervised clustering method developed to divide samples into two groups in gene expression data obtained through microarrays, selecting important genes simultaneously in the process. This has been found to be a better approach than conventional clustering methods like K-m...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/15734099113096660045
更新日期:2013-12-01 00:00:00
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journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409916666200504105249
更新日期:2020-05-03 00:00:00
abstract:BACKGROUND:Gefitinib (lressa) is the most prescribed drug, highly effective to treat nonsmall cell lung cancer; primarily it was considered that targeted therapy is a kinase inhibitor. The nonsmall cell lung cancer is caused by mutation in the Epithelial Growth Factor Receptor (EGFR) gene. Iressa works by blocking the ...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409914666180228111433
更新日期:2018-01-01 00:00:00
abstract::The design of inhibitors specific for one relevant carbonic anhydrase isozyme is the major challenge in the new therapeutic agents development. Comparative computational chemical structure and biological activity relationship studies on a series of carbonic anhydrase II inhibitors, benzenesulfonamide derivatives, bear...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409911666150916092624
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:The accuracy of molecular conformation for Quantitative Structure Activity Relationship (QSAR) studies is an important criteria, and the most favourable bioactive conformer selection is a tough task. Correct ligand alignment as input for 3D-QSAR is an important step that is prone to human biases. Multiple-di...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409913666170119115841
更新日期:2017-01-01 00:00:00
abstract:AIM:The aim of the study was to find out the role of auranofin as a promising broad spectrum antibacterial agent. METHODS:In-vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In-silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1386207323666200717155640
更新日期:2020-07-17 00:00:00
abstract::The first step in the process of drug development is to determine those lead compounds that demonstrate significant biological activity with regard to a target protein. Because this process is often costly and time consuming, there is a need to develop efficient methodologies for the generation of lead compounds for p...
journal_title:Current computer-aided drug design
pub_type: 杂志文章,评审
doi:10.2174/157340911793743556
更新日期:2011-03-01 00:00:00
abstract:INTRODUCTION:Acetyl-CoA Carboxylases (ACC) have been an important target for the therapy of metabolic syndrome, such as obesity, hepatic steatosis, insulin resistance, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), type 2 diabetes (T2DM), and some other diseases. METHODS...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409914666181109110030
更新日期:2019-01-01 00:00:00
abstract::A new mathematical approach is proposed in the definition of molecular descriptors (MDs) based on the application of information theory concepts. This approach stems from a new matrix representation of a molecular graph (G) which is derived from the generalization of an incidence matrix whose row entries correspond to...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409911309020003
更新日期:2013-06-01 00:00:00
abstract:INTRODUCTION:Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time exp...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409916666200625142447
更新日期:2020-06-25 00:00:00
abstract:BACKGROUND:Quantitative structure-activity relationship (QSAR) models can be used as a predictive tool for virtual screening of chemical libraries to identify novel drug candidates. The aims of this paper were to report the results of a study performed for descriptor selection, QSAR model development, and virtual scree...
journal_title:Current computer-aided drug design
pub_type: 杂志文章
doi:10.2174/1573409912666160414104902
更新日期:2016-01-01 00:00:00