Metal complexes as a promising source for new antibiotics.

Area of Science:

• Medicinal Chemistry
• Inorganic Chemistry
• Antimicrobial Research

Background:

• Antibiotic resistance is a critical global health threat, necessitating novel antimicrobial drug discovery.
• The current drug pipeline lacks diversity, with few new classes of antibiotics available.
• Metal complexes are explored for various diseases, but their antimicrobial potential is underexplored.

Purpose of the Study:

• To evaluate a large library of metal-containing compounds for antimicrobial activity.
• To identify novel metal-based antimicrobial agents with low cytotoxicity.
• To explore the potential of metal complexes in combating antibiotic resistance.

Main Methods:

• Screening of 906 metal-containing compounds from the Community for Open Antimicrobial Drug Discovery (CO-ADD) database.
• Testing compounds against various bacterial and fungal strains.
• Assessing cytotoxicity against mammalian cell lines and hemolytic properties.

Main Results:

• Metal-bearing compounds exhibited a significantly higher hit rate (9.9%) compared to organic molecules (0.87%).
• 88 compounds showed antimicrobial activity, including against fungi, without significant cytotoxicity.
• 30 compounds, including those with Mn, Co, Zn, Ru, Ag, Eu, Ir, and Pt, demonstrated potent activity against Gram-positive and/or Gram-negative bacteria, some in the nanomolar range against MRSA.

Conclusions:

• Metal-containing compounds represent a diverse and underexplored resource for antimicrobial drug discovery.
• This study identified numerous novel metal-based antimicrobial candidates with potential to address antibiotic resistance.
• Further investigation into these metal complexes could lead to the development of new classes of antibiotics.