Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Similarity-based Virtual Screening to Find Antituberculosis Agents based on Novel Scaffolds

Ángela García-García
,
Jesus Vicente de Julián-Ortiz
* ORCID logo ,
Jorge Gálvez
ORCID logo ,
David Font
,
Carles Ayats
,
María del Remedio Guna Serrano
,
Carlos Muñoz-Collado
,
Rafael Borrás
,
José Manuel Villalgordo
Version 1 : Received: 7 September 2022 / Approved: 14 September 2022 / Online: 14 September 2022 (03:32:55 CEST)

A peer-reviewed article of this Preprint also exists.

García-García, Á.; Julián-Ortiz, J.V.; Gálvez, J.; Font, D.; Ayats, C.; Guna Serrano, M.R.; Muñoz-Collado, C.; Borrás, R.; Villalgordo, J.M. Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays. Int. J. Mol. Sci. 2022, 23, 15057. García-García, Á.; Julián-Ortiz, J.V.; Gálvez, J.; Font, D.; Ayats, C.; Guna Serrano, M.R.; Muñoz-Collado, C.; Borrás, R.; Villalgordo, J.M. Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays. Int. J. Mol. Sci. 2022, 23, 15057.

Abstract

A method is developed to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC). A structurally heterogeneous set of compounds active against MTBC was used to obtain a structural pattern model based on structural invariants. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets and was also able to select new active chemical structures in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]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.

Keywords

MTBC; virtual screening; topological indices; linear discriminant analysis; pharmacological activity distribution diagrams; antimicrobial drugs; drug design

Subject

Chemistry and Materials Science, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.