The evaluation of the anti-cancer drug elesclomol that forms a redox-active copper chelate as a potential anti-tubercular drug.
IUBMB Life
; 71(5): 532-538, 2019 05.
Article
in En
| MEDLINE
| ID: mdl-30698324
ABSTRACT
The observations that the innate immune system employs copper to eliminate bacterial infection and that resistance to copper enhances virulence of Mycobacterium tuberculosis (Mtb) prompted us to examine the effects the anti-cancer agent elesclomol on Mtb. As a bis-thionohydrazide, elesclomol chelates with copper to form a copper complex in situ that via redox cycling of the metal ion greatly enhances oxidative stress in tumour cells. Here, we demonstrate that elesclomol is relatively potent against Mtb H37Rv with minimum inhibitory concentration of 10 µM (4 mg/L) and against multidrug resistant clinical isolates of Mtb, displays additive interactions with known tuberculosis drugs such as isoniazid and ethambutol, and a synergistic interaction with rifampicin. Controlled supplementation of elesclomol with copper in culture medium increased Mtb sensitivity by >65 fold. Overall, the activities of elesclomol in principle indicate the possibility of repurposing elesclomol or designing new thionohydrazides as potential drugs for use against Mtb. © 2019 IUBMB Life, 71(5)532-538, 2019.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tuberculosis
/
Chelating Agents
/
Copper
/
Hydrazines
/
Mycobacterium tuberculosis
/
Antineoplastic Agents
/
Antitubercular Agents
Type of study:
Evaluation_studies
Limits:
Humans
Language:
En
Journal:
IUBMB Life
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2019
Type:
Article
Affiliation country:
South Africa