Osmium-arene complexes with high potency towards Mycobacterium tuberculosis

Area of Science:

• Metallomics and Medicinal Chemistry
• Antimicrobial Drug Discovery

Background:

• Tuberculosis (TB) treatment is challenged by increasing drug resistance in Mycobacterium tuberculosis (Mtb).
• Novel antitubercular agents with distinct mechanisms of action are urgently required to address this global health crisis.

Purpose of the Study:

• To screen a series of organometallic half-sandwich Os(II) complexes for activity against Mtb.
• To compare the efficacy and toxicity of these complexes against Mtb and normal human lung cells (MRC5).
• To identify potential new drug candidates for tuberculosis treatment.

Main Methods:

• Screening of 17 distinct half-sandwich Os(II) complexes with varying arenes and substituents.
• Determination of minimum inhibitory concentrations (MIC) against Mtb and cytotoxicity against MRC5 cells.
• Investigation of osmium uptake and mechanism of action in Mtb.

Main Results:

• Several Os(II) complexes demonstrated potent activity against Mtb, with MIC values as low as 1.25 µM.
• Monodentate iodido complexes were generally more potent than chlorido counterparts.
• The most active complex, a p-cymene Os(II) NMe2-phenyl-azopyridine iodido complex, also showed activity against cancer cells.

Conclusions:

• Half-sandwich organo-osmium(II) complexes represent a promising class of compounds for developing new antitubercular agents.
• The observed activity suggests a redox mechanism of action involving intracellular thiols, common to both Mtb and human cells.
• Further development of these complexes could lead to novel treatments for drug-resistant tuberculosis.