Molecular Topology for the Discovery of New Broad-Spectrum Antibacterial Drugs

Bueso-Bordils, José I.; Alemán‐López, Pedro; Suay-García, Beatriz; Martín-Algarra, Rafael; Duart, María J.; Falcó, Antonio; Antón-Fos, G.M.

doi:10.3390/biom10091343

Cited by 4 publications

(3 citation statements)

References 30 publications

(32 reference statements)

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“…Topological indices are two-dimensional descriptors derived from the topological representation of a molecule. In recent decades, molecular topology has emerged as a powerful approach to evaluate structure-activity relationships [23], especially in the fields of pharmacology and toxicology [24,25]. According to this approach, molecular structures are described in terms of the mathematical properties of their associated graphs.…”

Section: Correlation Of Water Activity Datamentioning

confidence: 99%

Water Activity Prediction in Sugar and Polyol Systems Using Theoretical Molecular Descriptors

Zuorro

2021

IJMS

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Water activity is a key factor in the development of pharmaceutical, cosmetic, and food products. In aqueous solutions of nonelectrolytes, the Norrish model provides a simple and effective way to evaluate this quantity. However, it contains a parameter, known as the Norrish constant, that must be estimated from experimental data. In this study, a new strategy is proposed for the prediction of water activity in the absence of experimental information, based on the use of theoretical molecular descriptors for characterizing the effects of a solute. This approach was applied to the evaluation of water activity in the presence of sugars (glucose, fructose, xylose, sucrose) and polyols (sorbitol, xylitol, glycerol, erythritol). The use of two descriptors related to the constitutional and connectivity properties of the solutes was first investigated. Subsequently, a new theoretical descriptor, named the global information index (G), was developed. By using this index, the water activity curves in the binary systems were reconstructed. The positive results obtained support the proposed strategy, as well as the possibility of including, in a single information index, the main molecular features of a solute that determine its effects on water activity.

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Section: Correlation Of Water Activity Datamentioning

confidence: 99%

Water Activity Prediction in Sugar and Polyol Systems Using Theoretical Molecular Descriptors

Zuorro

2021

IJMS

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“…The effectiveness of the topological method has also been proven, having been successfully applied to different therapeutic groups, such as anti-HIV [ 29 ], antihistaminic [ 30 ], antitumor [ 31 ], anti-Alzheimer [ 32 ], and antibacterial agents [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Topology for the Search of New Anti-MRSA Compounds

Bueso-Bordils

Alemán‐López

Martín-Algarra

et al. 2021

IJMS

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The variability of methicillin-resistant Staphylococcus aureus (MRSA), its rapid adaptive response against environmental changes, and its continued acquisition of antibiotic resistance determinants have made it commonplace in hospitals, where it causes the problem of multidrug resistance. In this study, we used molecular topology to develop several discriminant equations capable of classifying compounds according to their anti-MRSA activity. Topological indices were used as structural descriptors and their relationship with anti-MRSA activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds. Four extra equations were constructed, named DFMRSA1, DFMRSA2, DFMRSA3 and DFMRSA4 (DFMRSA was built in a previous study), all with good statistical parameters, such as Fisher–Snedecor F (>68 in all cases), Wilk’s lambda (<0.13 in all cases), and percentage of correct classification (>94% in all cases), which allows a reliable extrapolation prediction of antibacterial activity in any organic compound. The results obtained clearly reveal the high efficiency of combining molecular topology with LDA for the prediction of anti-MRSA activity.

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“…These methods, combined with molecular topology, constitute a time-and cost-effective option to tackle drug discovery. In fact, molecular topology is especially interesting because the models built using molecular topology indices can be applied to databases with structural diversity, as the selection of active compounds is carried out taking only into account the mathematical-topological similarity [12]. As a consequence, the theoretically active compounds selected by these models will possess similar pharmacokinetic and pharmacodynamic properties, regardless of its structural family.…”

Section: Introductionmentioning

confidence: 99%

Tree-Based QSAR Model for Drug Repurposing in the Discovery of New Antibacterial Compounds against Escherichia coli

et al. 2020

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Drug repurposing appears as an increasing popular tool in the search of new treatment options against bacteria. In this paper, a tree-based classification method using Linear Discriminant Analysis (LDA) and discrete indexes was used to create a QSAR (Quantitative Structure-Activity Relationship) model to predict antibacterial activity against Escherichia coli. The model consists on a hierarchical decision tree in which a discrete index is used to divide compounds into groups according to their values for said index in order to construct probability spaces. The second step consists in the calculation of a discriminant function which determines the prediction of the model. The model was used to screen the DrugBank database, identifying 134 drugs as possible antibacterial candidates. Out of these 134 drugs, 8 were antibacterial drugs, 67 were drugs approved for different pathologies and 55 were drugs in experimental stages. This methodology has proven to be a viable alternative to the traditional methods used to obtain prediction models based on LDA and its application provides interesting new drug candidates to be studied as repurposed antibacterial treatments. Furthermore, the topological indexes Nclass and Numhba have proven to have the ability to group active compounds effectively, which suggests a close relationship between them and the antibacterial activity of compounds against E. coli.

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Molecular Topology for the Discovery of New Broad-Spectrum Antibacterial Drugs

Cited by 4 publications

References 30 publications

Water Activity Prediction in Sugar and Polyol Systems Using Theoretical Molecular Descriptors

Water Activity Prediction in Sugar and Polyol Systems Using Theoretical Molecular Descriptors

Molecular Topology for the Search of New Anti-MRSA Compounds

Tree-Based QSAR Model for Drug Repurposing in the Discovery of New Antibacterial Compounds against Escherichia coli

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