6533b858fe1ef96bd12b6295
RESEARCH PRODUCT
Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays
ÁNgela García-garcíaJesus Vicente De Julián-ortizJorge GálvezDavid FontCarles AyatsMaría Del Remedio Guna SerranoCarlos Muñoz-colladoRafael BorrásJosé Manuel Villalgordosubject
Inorganic ChemistryOrganic ChemistryMicrobiologiaMicrobiologia mèdicaFísicaGeneral MedicinePhysical and Theoretical ChemistryMTBC; virtual screening; topological indices; linear discriminant analysis; pharmacological activity distribution diagrams; antimicrobial drugs; drug designMolecular BiologySpectroscopyCatalysisComputer Science Applicationsdescription
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-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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-12-01 | International Journal of Molecular Sciences |