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

Abstract

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.

Biocompatible 3D-Printed Tendon/Ligament Scaffolds Based on Polylactic Acid/Graphite Nanoplatelet Composites

“…We believe that this article presents compelling in vitro results for further in vivo experiments. Some strategies may be considered for future directions of this research, to improve the scaffolds’ overall performance and clinical applications, namely, their capability to inhibit mycobacteria [ 71 ] or even adapt and change over time [ 72 ].…”