Search results for "QSAR"
showing 10 items of 48 documents
Dry selection and wet evaluation for the rational discovery of new anthelmintics
2017
Helminths infections remain a major problem in medical and public health. In this report, atom-based 2D bilinear indices, a TOMOCOMD-CARDD (QuBiLs-MAS module) molecular descriptor family and linear discriminant analysis (LDA) were used to find models that differentiate among anthelmintic and non-anthelmintic compounds. Two classification models obtained by using non-stochastic and stochastic 2D bilinear indices, classified correctly 86.64% and 84.66%, respectively, in the training set. Equation 1(2) correctly classified 141(135) out of 165 [85.45%(81.82%)] compounds in external validation set. Another LDA models were performed in order to get the most likely mechanism of action of anthelmin…
An Integrated Pharmacophore/Docking/3D-QSAR Approach to Screening a Large Library of Products in Search of Future Botulinum Neurotoxin A Inhibitors
2020
Botulinum toxins are neurotoxins produced by Clostridium botulinum. This toxin can be lethal for humans as a cause of botulism
Identification of estrogen receptor α ligands with virtual screening techniques.
2016
Utilization of computer-aided molecular discovery methods in virtual screening (VS) is a cost-effective approach to identify novel bioactive small molecules. Unfortunately, no universal VS strategy can guarantee high hit rates for all biological targets, but each target requires distinct, fine-tuned solutions. Here, we have studied in retrospective manner the effectiveness and usefulness of common pharmacophore hypothesis, molecular docking and negative image-based screening as potential VS tools for a widely applied drug discovery target, estrogen receptor α (ERα). The comparison of the methods helps to demonstrate the differences in their ability to identify active molecules. For example,…
Investigation on Quantitative Structure-Activity Relationships of 1,3,4-Oxadiazole Derivatives as Potential Telomerase Inhibitors.
2020
Background:Telomerase, a reverse transcriptase, maintains telomere and chromosomes integrity of dividing cells, while it is inactivated in most somatic cells. In tumor cells, telomerase is highly activated, and works in order to maintain the length of telomeres causing immortality, hence it could be considered as a potential marker to tumorigenesis.A series of 1,3,4-oxadiazole derivatives showed significant broad-spectrum anticancer activity against different cell lines, and demonstrated telomerase inhibition.Methods:This series of 24 N-benzylidene-2-((5-(pyridine-4-yl)-1,3,4-oxadiazol-2yl)thio)acetohydrazide derivatives as telomerase inhibitors has been considered to carry out QSAR studies…
Recent advances on CDK inhibitors: An insight by means of in silico methods
2017
The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…
Innovative Strategies to Develop Chemical Categories Using a Combination of Structural and Toxicological Properties.
2016
Interest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g., the European Union's Cosmetic Directive and REACH, demands the use of alternative methods. Frameworks, such as the Read-across Assessment Framework or the Adverse Outcome Pathway Knowledge Base, support the development of these methods. The aim of the project presented in this publication was to develop substance categories for a read-across with complex endpoints of toxicity based on existing databases. The basic conceptual approach was to combine str…
QuBiLS-MAS, open source multi-platform software for atom- and bond-based topological (2D) and chiral (2.5D) algebraic molecular descriptors computati…
2017
Background In previous reports, Marrero-Ponce et al. proposed algebraic formalisms for characterizing topological (2D) and chiral (2.5D) molecular features through atom- and bond-based ToMoCoMD-CARDD (acronym for Topological Molecular Computational Design-Computer Aided Rational Drug Design) molecular descriptors. These MDs codify molecular information based on the bilinear, quadratic and linear algebraic forms and the graph-theoretical electronic-density and edge-adjacency matrices in order to consider atom- and bond-based relations, respectively. These MDs have been successfully applied in the screening of chemical compounds of different therapeutic applications ranging from antimalarials…
Diseño por Topología molecular y ensayos farmacológicos de nuevos inhibidores frente a WNT/β-CATENINA Y PI3K/Akt/mTOR
2015
El cáncer colorrectal y el de próstata causan una elevadísima tasa de muerte a nivel mundial. Por lo que, cualquier estrategia para detener o al menos reducir su desarrollo y progresión sería una importante contribución en la investigación actual. Por todo ello, el objetivo principal de la presente Tesis es la identificación de nuevos agentes quimiopreventivos frente al cáncer, que actúen modulando dos de las vías más implicadas en su desarrollo: PI3K/Akt/mTOR y Wnt/β-catenina. Hoy en día, existen diferentes enfoques para el descubrimiento de nuevos hits and leads, pero esta Tesis se centra en la metodología de la Topología Molecular, que ya ha demostrado su extraordinaria eficacia en este …
QuBiLs-MAS method in early drug discovery and rational drug identification of antifungal agents
2015
The QuBiLs-MAS approach is used for the in silico modelling of the antifungal activity of organic molecules. To this effect, non-stochastic (NS) and simple-stochastic (SS) atom-based quadratic indices are used to codify chemical information for a comprehensive dataset of 2478 compounds having a great structural variability, with 1087 of them being antifungal agents, covering the broadest antifungal mechanisms of action known so far. The NS and SS index-based antifungal activity classification models obtained using linear discriminant analysis (LDA) yield correct classification percentages of 90.73% and 92.47%, respectively, for the training set. Additionally, these models are able to correc…
Aplicación de la topología molecular para la predicción de biodegradación anaerobia de clorofenoles
2013
Se ha aplicado la topología molecular y el análisis de regresión multilineal en la búsqueda de un modelo de relación cuantitativa estructura-actividad (QSAR) capaz de predecir la capacidad de biodegradación anaerobia de un grupo de clorofenoles. Tomando el valor de la constante de velocidad de desaparición del derivado clorofenolico, log k, como variable dependiente y los descriptores topológicos como variables independientes, se obtuvo una ecuación con tres variables y coeficientes de correlación y de predicción , R2=0.9291 y Q2=0.870. El modelo fue validado a través de una validación interna y un test de aleatoriedad. Los resultados obtenidos muestran una alta capacidad de predicción para…