Multifunctional Enzymes as Targets for the Treatment of Tuberculosis: Paving the Way for New Anti-TB Drugs

• Type: Another Publication in an International Scientific Journal
• Date: 2021

Authors

Teixeira, CSS (Author) Other; Cerqueira, NMFSA (Author) Other; Sergio Filipe Sousa (Author) FCUP

Journal

Title: Current Medicinal Chemistry

Vol. 28

Pages: 5847-5882

ISSN: 0929-8673

Publisher: Bentham Science

Indexing

ISI Web of Knowledge - 4 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00T-WKS

DOI: 10.2174/0929867328666201229122722

Abstract (EN): In spite of the medical and technological developments of the last centuries, Tuberculosis (TB) has remained a challenging disease, with a limited number of therapeutic options, particularly in light of the increase in drug-resistant cases. The search for new molecules continues, with several candidates currently in clinical testing and ongoing efforts to identify novel targets. This work summarizes recent developments on anti-TB therapy, starting by discussing the current epidemiologic status and presenting an overview of the history of anti-tuberculosis drug discovery. Special attention is dedicated to five multifunctional enzymes that are regarded as promising targets for new anti-TB drugs: 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase (ATIC); 3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBPS)/GTP cyclohydrolase II (GCHII); glutamine dependent NAD+ Synthetase (NadE); chorismate synthase (CS); and Tryptophan synthase (TS). These enzymes are involved in metabolic pathways critical for the M. tuberculosis survival, growth or replication, but that are not expressed in humans or have significant differences in terms of functionality, which makes them appealing targets. Their function, structure, possible catalytic mechanisms, and current inhibition strategies and inhibitors are reviewed and discussed.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 36