Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays

A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated thr...

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Published in:International journal of molecular sciences 2022-12, Vol.23 (23), p.15057
Main Authors: García-García, Ángela, Julián-Ortiz, Jesus Vicente de, Gálvez, Jorge, Font, David, Ayats, Carles, Guna Serrano, María Del Remedio, Muñoz-Collado, Carlos, Borrás, Rafael, Villalgordo, José Manuel
Format: Article
Language:English
Subjects:
Antitubercular Agents - chemistry
Antitubercular Agents - pharmacology
Classification
Databases, Factual
Discriminant analysis
Drug Design
Identification methods
Mathematical models
Molecular Structure
Probability
Pyrimidines
Quantitative Structure-Activity Relationship
Scaffolds
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container_issue 23
container_start_page 15057
container_title International journal of molecular sciences
container_volume 23
creator García-García, Ángela
Julián-Ortiz, Jesus Vicente de
Gálvez, Jorge
Font, David
Ayats, Carles
Guna Serrano, María Del Remedio
Muñoz-Collado, Carlos
Borrás, Rafael
Villalgordo, José Manuel
description A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5- ]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.
doi_str_mv 10.3390/ijms232315057
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subjects Antitubercular Agents - chemistry
Antitubercular Agents - pharmacology
Classification
Databases, Factual
Discriminant analysis
Drug Design
Identification methods
Mathematical models
Molecular Structure
Probability
Pyrimidines
Quantitative Structure-Activity Relationship
Scaffolds
title Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays
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