Application of Bioinformatics for the Search of Novel Anti-Viral Therapies: Rational Design of Anti-Herpes Agents

Cordeiro, Alejandro Speck-Planche and M. Natalia D.S.

doi:10.2174/157489311795222392

Cited by 28 publications

(9 citation statements)

References 135 publications

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“…An important element of FCC and ACF descriptors is that they can be perfectly combined with other fragment-based descriptors in a model, and thereafter fragment contributions be calculated. This has been demonstrated in several QSAR studies [123][124][125][126].…”

Section: Functional Group Counts and Atom Centered-fragmentsmentioning

confidence: 55%

Role of Ligand-Based Drug Design Methodologies toward the Discovery of New Anti- Alzheimer Agents: Futures Perspectives in Fragment-Based Ligand Design

Speck‐Planche

Luan²,

Cordeiro³

2012

CMC

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Alzheimer's disease (AD), a degenerative disease affecting the brain, is the single most common source of dementia in adults. The cause and the progression of AD still remains a mystery among medical experts. As a result, a cure has not yet been discovered, even after decade's worth of research that started since 1906, when the disease was first identified. Despite the efforts of the scientific community, several of the biological receptors associated with AD have not been sufficiently studied to date, limiting in turn the design of new and more potent anti-AD agents. Thus, the search for new drug candidates as inhibitors of different targets associated with AD constitutes an essential part towards the discovery of new and more efficient anti-AD therapies. The present work is focused on the role of the Ligand-Based Drug Design (LBDD) methodologies which have been applied for the elucidation of new molecular entities with high inhibitory activity against targets related with AD. Particular emphasis is given also to the current state of fragment-based ligand approaches as alternatives of the Fragment-Based Drug Discovery (FBDD) methodologies. Finally, several guidelines are offered to show how the use of fragment-based descriptors can be determinant for the design of multi-target inhibitors of proteins associated with AD.

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Section: Functional Group Counts and Atom Centered-fragmentsmentioning

confidence: 55%

Role of Ligand-Based Drug Design Methodologies toward the Discovery of New Anti- Alzheimer Agents: Futures Perspectives in Fragment-Based Ligand Design

Speck‐Planche

Luan²,

Cordeiro³

2012

CMC

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“…Future perspectives in the discovery of flavonoids with anticancer activity may be focused on the use of novel and recently reported QSAR studies, which allow simultaneous prediction and virtual screening of compounds with the desired biological activity [24][25][26][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136]. These promising methodologies could be of great help in chemotaxonomic studies, the fast and efficient detection of flavonoids from different plant species, and at the same time, with the computer-aided selection of these versatile natural products as anticancer agents.…”

Section: Concluding Remarks and Future Perspec-tivesmentioning

confidence: 99%

SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review

Scotti

Mendonça²,

Moreira³

et al. 2013

CTMC

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Flavonoids are phenolic compounds, secondary metabolites of plants that cause several benefits to our health, including helping the treatment against cancer. These pharmacological properties are associated with the ability of flavonoids in attenuating the generation of reactive oxygen species, acting as chelate compounds or affecting the oxi-redox cycle. In spite of the large number of information in term of SAR and QSAR, no recent review has tabulated and discussed in detail these data. In view of this, we bring here a detailed discussion of the structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) models. We have also analyzed the correlation between the chemical structure of flavonoids and analogues to their anticancer activities. A large number of methodologies have been used to identify the characteristics of these compounds with their potential anticancer: multiple linear regression, principal components analysis, comparative molecular field analysis, comparative molecular similarity indices analysis, partial least squares, neural networks, configuration of classification and regression trees, Free-Wilson, docking; using topological, structural and enthalpies' descriptors. We also discussed the use of docking models, together with QSAR models, for the virtual screening of anticancer flavonoids. The importance of docking models to the medicinal chemistry of anticancer flavonoids has increased in the last decade, especially to help in identifying the structural determinants responsible for the activity. We tabulated here the most important examples of virtual screening determined for anticancer flavonoids and we highlighted the structural determinants. The mode of action, the most potent anticancer flavonoids and hints for the structural design of anticancer flavonoids are revised in details and provided here.

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“…We can write a general linear equation for an LDA-based QSPR-like model with the parameters mentioned above. In general, this type of LDA-based QSPR/QSAR models has been used before for many research studies, mainly for small molecules (Casanola-Martin et al, 2006Estrada et al, 2001Estrada et al, , 2002Estrada et al, , 2006Estrada et al, , 2010Marrero-Ponce et al, 2007a,b, 2010Speck-Planche and Cordeiro, 2011;Speck-Planche et al, 2009, 2011aVilar et al, 2005). The LDA model based on the new Rücker-Markov indices is shown in the following formula:…”

Section: Linear Discriminant Analysis (Lda) Modelsmentioning

confidence: 99%

The Rücker–Markov invariants of complex Bio-Systems: Applications in Parasitology and Neuroinformatics

2013

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Rücker's walk count (WC) indices are well-known topological indices (TIs) used in Chemoinformatics to quantify the molecular structure of drugs represented by a graph in Quantitative structure-activity/property relationship (QSAR/QSPR) studies. In this work, we introduce for the first time the higher-order (kth order) analogues (WCk) of these indices using Markov chains. In addition, we report new QSPR models for large complex networks of different Bio-Systems useful in Parasitology and Neuroinformatics. The new type of QSPR models can be used for model checking to calculate numerical scores S(Lij) for links Lij (checking or re-evaluation of network connectivity) in large networks of all these fields. The method may be summarized as follows: (i) first, the WCk(j) values are calculated for all jth nodes in a complex network already created; (ii) A linear discriminant analysis (LDA) is used to seek a linear equation that discriminates connected or linked (Lij=1) pairs of nodes experimentally confirmed from non-linked ones (Lij=0); (iii) The new model is validated with external series of pairs of nodes; (iv) The equation obtained is used to re-evaluate the connectivity quality of the network, connecting/disconnecting nodes based on the quality scores calculated with the new connectivity function. The linear QSPR models obtained yielded the following results in terms of overall test accuracy for re-construction of complex networks of different Bio-Systems: parasite-host networks (93.14%), NW Spain fasciolosis spreading networks (71.42/70.18%) and CoCoMac Brain Cortex co-activation network (86.40%). Thus, this work can contribute to the computational re-evaluation or model checking of connectivity (collation) in complex systems of any science field.

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Application of Bioinformatics for the Search of Novel Anti-Viral Therapies: Rational Design of Anti-Herpes Agents

Cited by 28 publications

References 135 publications

Role of Ligand-Based Drug Design Methodologies toward the Discovery of New Anti- Alzheimer Agents: Futures Perspectives in Fragment-Based Ligand Design

Role of Ligand-Based Drug Design Methodologies toward the Discovery of New Anti- Alzheimer Agents: Futures Perspectives in Fragment-Based Ligand Design

SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review

The Rücker–Markov invariants of complex Bio-Systems: Applications in Parasitology and Neuroinformatics

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