Search for Inhibitors of Mycobacterium tuberculosis Transketolase in a Series of Sulfo-Substituted Compounds

I V Gushchina; D K Nilov; T A Shcherbakova; S M Baldin; V K Švedas

doi:10.32607/actanaturae.15709

Search for Inhibitors of Mycobacterium tuberculosis Transketolase in a Series of Sulfo-Substituted Compounds

Acta Naturae. 2023 Apr-Jun;15(2):81-83. doi: 10.32607/actanaturae.15709.

Authors

I V Gushchina¹, D K Nilov², T A Shcherbakova², S M Baldin², V K Švedas^{1

2}

Affiliations

¹ Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, 119234 Russian Federation.
² Lomonosov Moscow State University, Belozersky Institute of Physicochemical Biology, Moscow, 119234 Russian Federation.

Abstract

As a result of the computer screening of a library of sulfo-substituted compounds, molecules capable of binding to the active site of transketolase from Mycobacterium tuberculosis were identified. An experimental verification of the inhibitory activity of the most promising compound, STK045765, against a highly purified recombinant enzyme preparation was carried out. It was shown that the STK045765 molecule competes for the binding site of the pyrophosphate group of the thiamine diphosphate cofactor and, at a micromolar concentrations, is able to suppress the activity of mycobacterial transketolase. The discovered furansulfonate scaffold may serve as the basis for the creation of anti-tuberculosis drugs.

Keywords: brain; intravenous transplantation; ischemia/reperfusion; mesenchymal stem cells; microvascular density; perfusion; reactivity.