Antimicrobial Pyridazines: Synthesis, Characterization, Cytotoxicity, Substrate Promiscuity, and Molecular Docking

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Antimicrobial Agents

Background:

• Pyridazine derivatives are recognized for their diverse biological activities.
• Development of novel antimicrobial agents is crucial to combat rising resistance.
• Efficient synthetic routes are needed for new drug discovery.

Purpose of the Study:

• To synthesize novel pyridazine derivatives.
• To evaluate their antimicrobial potential against various bacterial and fungal strains.
• To assess their drug-likeness and safety profile.

Main Methods:

• Facile synthesis involving hydrazide coupling and cyclization.
• Structural confirmation using spectroscopic techniques (IR, NMR) and LC/MS.
• Antimicrobial screening, ADME/pharmacokinetic prediction, cytotoxicity assays, and molecular docking.

Main Results:

• Successful synthesis of new pyridazine derivatives.
• Strong to very strong antibacterial activity against Gram-negative bacteria (e.g., E. coli, P. aeruginosa).
• Chloro derivatives showed superior activity compared to chloramphenicol; no significant antifungal activity observed.
• Favorable ADME predictions, low cytotoxicity (IC50 >64 μg/mL), and good docking interactions with E. coli DNA gyrase.

Conclusions:

• The synthesized pyridazines are effective antibacterial agents, particularly against Gram-negative pathogens.
• These compounds possess drug-like properties and a good safety profile, indicating potential as therapeutic candidates.
• Further investigation into these pyridazine derivatives is warranted for antimicrobial drug development.