Multinuclear NMR analysis of the antitubercular drug ethionamide

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Nuno Vale (Author) ICBAS; Correia, A (Author) Other; Figueiredo, P (Author) Other; Santos, HA (Author) Other

Journal

Title: Journal of Molecular Structure

Vol. 1105

Pages: 286-292

ISSN: 0022-2860

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Other information

Authenticus ID: P-00J-FN2

DOI: 10.1016/j.molstruc.2015.10.047

Abstract (EN): Tuberculosis remains as the deadliest bacterial infection in developing countries, a situation that is particularly aggravated by the increasing spread of multidrug resistant mycobacteria (MDR-TB). In this view, not only new anti-tubercular drugs are urgently needed, but also a better understanding of the existing ones may aid in the future design of more efficient derivatives or surrogates. Ethionamide (ETA) is an anti-tubercular pro-drug used as second-line therapy against MDR-TB, being bio-activated by the mycobacterial monooxygenase EtA. ETA has been the focus of several research works, devoted either to the identification of ETA's metabolites or to the development of novel derivatives potentially useful to fight against tuberculosis. In either case, structural analysis of ETA and related structures is of undeniable relevance, while the presence of sulfur in ETA's structure brings about the possibility of including 33SNMR in the toolbox of structural analysis techniques. In this work, we have engaged into a multinuclear NMR characterization of ETA, through the study of the drug's solubility in seven deuterated solvents, and of the chemical shifts for different nuclei in ETA. Results showed which are the best conditions to study ETA by NMR and provided some important evidence on the low reactivity of the drug's thioamide group, which may be of relevance for future drug derivatization approaches.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7