Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.



A bioinorganic chemistry perspective on the roles of metals as drugs and targets against Mycobacterium tuberculosis – a journey of opportunities

Author affiliations

Abstract

Medicinal inorganic chemists have provided many strategies to tackle a myriad of diseases, pushing forward the frontiers of pharmacology. As an example, the fight against tuberculosis (TB), an infectious bacterial disease, has led to the development of metal-based compounds as potential drugs. This disease remains a current health issue causing over 1.4 million of deaths per year. The emergence of multi- (MDR) and extensively-drug resistant (XDR) Mycobacterium tuberculosis (Mtb) strains along with a long dormancy process, place major challenges in developing new therapeutic compounds. Isoniazid is a front-line prodrug used against TB with appealing features for coordination chemists, which have been explored in a series of cases reported here. An isoniazid iron-based compound, called IQG-607, has caught our attention, whose in vitro and in vivo studies are advanced and thoroughly discussed, along with other metal complexes. Isoniazid is inactive against dormant Mtb, a hard to eliminate state of this bacillus, found in one-fourth of the world's population and directly implicated in the lengthy treatment of TB (ca. 6 months). Thus, our understanding of this phenomenon may lead to a rational design of new drugs. Along these lines, we describe how metals as targets can cross paths with metals used as selective therapeutics, where we mainly review heme-based sensors, DevS and DosT, as a key system in the Mtb dormancy process and a current drug target. Overall, we report new opportunities for bioinorganic chemists to tackle this longstanding and current threat.

Graphical abstract: A bioinorganic chemistry perspective on the roles of metals as drugs and targets against Mycobacterium tuberculosis – a journey of opportunities

Back to tab navigation

Article information


Submitted
14 Apr 2020
Accepted
01 Jun 2020
First published
01 Jun 2020

Dalton Trans., 2020, Advance Article
Article type
Perspective

A bioinorganic chemistry perspective on the roles of metals as drugs and targets against Mycobacterium tuberculosis – a journey of opportunities

L. G. F. Lopes, E. M. Carvalho and E. H. S. Sousa, Dalton Trans., 2020, Advance Article , DOI: 10.1039/D0DT01365J

Social activity

Search articles by author

Spotlight

Advertisements