Dihydropyrimidinones Against Multiresistant Bacteria

Area of Science:

• Medicinal Chemistry
• Microbiology
• Drug Discovery

Background:

• Increasing bacterial resistance to antimicrobials is a critical global health issue, leading to high morbidity and mortality rates.
• There is an urgent need for novel antimicrobial substances to combat infections caused by multidrug-resistant (MDR) bacteria.
• Identified target pathogens include MDR Gram-negative bacilli (e.g., *Acinetobacter baumannii*, *Escherichia coli*, *Pseudomonas aeruginosa*) and Gram-positive cocci (e.g., *Enterococcus faecium*, *Staphylococcus aureus*).

Purpose of the Study:

• To synthesize and evaluate the in vitro antimicrobial activity of novel compounds.
• To assess the cytotoxicity of the synthetic compounds.
• To explore the potential of dihydropyrimidinone (DHPM) derivatives as future antimicrobial agents.

Main Methods:

• Antibacterial activity was determined by measuring minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using broth microdilution and agar plating.
• Chemical characterization involved melting point determination and gas chromatography-mass spectrometry (GC-MS).
• Cytotoxicity was evaluated by assessing cell viability at various compound concentrations.

Main Results:

• Synthetic compounds exhibited antimicrobial activity against Gram-positive cocci (MICs 0.16–80 μg/ml) and Gram-negative bacilli (MICs 23.2–80 μg/ml).
• *Enterococcus faecium* and *Staphylococcus aureus* showed the most favorable MIC values.
• Cytotoxicity tests revealed no significant adverse effects on cell viability across tested concentrations (5, 20, and 80 μg/ml).

Conclusions:

• The synthesized DHPM derivatives demonstrate significant in vitro antimicrobial potential against a range of MDR bacteria.
• The compounds exhibit a favorable safety profile with no significant cytotoxicity observed.
• DHPM derivatives represent a promising alternative for the development of novel antimicrobial drugs to address the challenge of antimicrobial resistance.