Deciphering the mechanism of action of antitubercular compounds with metabolomics

Isin T Sakallioglu; Raúl G Barletta; Patrick H Dussault; Robert Powers

doi:10.1016/j.csbj.2021.07.034

Deciphering the mechanism of action of antitubercular compounds with metabolomics

Comput Struct Biotechnol J. 2021 Jul 30:19:4284-4299. doi: 10.1016/j.csbj.2021.07.034. eCollection 2021.

Authors

Isin T Sakallioglu¹, Raúl G Barletta², Patrick H Dussault¹, Robert Powers^{1

3}

Affiliations

¹ Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA.
² School of Veterinary Medicine and Biomedical Sciences, University of Nebraska Lincoln, Lincoln, NE 68583-0905, USA.
³ Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA.

Abstract

Tuberculosis (TB), one of the oldest and deadliest bacterial diseases, continues to cause serious global economic, health, and social problems. Current TB treatments are lengthy, expensive, and routinely ineffective against emerging drug resistant strains. Thus, there is an urgent need for the identification and development of novel TB drugs possessing comprehensive and specific mechanisms of action (MoAs). Metabolomics is a valuable approach to elucidating the MoA, toxicity, and potency of promising chemical leads, which is a critical step of the drug discovery process. Recent advances in metabolomics methodologies for deciphering MoAs include high-throughput screening techniques, the integration of multiple omics methods, mass spectrometry imaging, and software for automated analysis. This review describes recently introduced metabolomics methodologies and techniques for drug discovery, highlighting specific applications to the discovery of new antitubercular drugs and the elucidation of their MoAs.

Keywords: Antitubercular drugs; Drug discovery; Mechanisms of action; Metabolomics; Multi-drug resistant tuberculosis; Pharmacometabolomics; Tuberculosis.

Publication types

Review