New Triazole-Isoxazole Hybrids as Antibacterial Agents: Design, Synthesis, Characterization, In Vitro, and In Silico...

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Computational Chemistry

Background:

• Emerging antibiotic resistance necessitates the development of novel antibacterial agents.
• Isoxazole and triazole moieties are known pharmacophores with diverse biological activities.

Purpose of the Study:

• To synthesize novel isoxazole-triazole conjugates.
• To evaluate the in vitro antibacterial activity of synthesized compounds.
• To investigate the mechanism of action and pharmacokinetic properties of promising candidates.

Main Methods:

• Multi-step synthesis of isoxazole-triazole conjugates starting from 3-formylchromone.
• Structural characterization using NMR (¹H, ¹³C) and Mass Spectrometry (MS).
• Antibacterial screening against *Staphylococcus aureus* and *Escherichia coli* strains, including clinical isolates.
• Minimum Bactericidal Concentration (MBC) determination.
• ADMET pharmacokinetic profiling.
• Molecular docking and molecular dynamics simulations.

Main Results:

• Efficient synthesis of novel isoxazole-triazole conjugates was achieved.
• Compound 7b demonstrated superior antibacterial activity against *Escherichia coli* ATCC 25922 and *Pseudomonas aeruginosa* compared to standard antibiotics.
• Compound 7b exhibited a bactericidal effect on *Escherichia coli* ATCC 25922.
• Favorable ADMET profile and good oral bioavailability were observed for compound 7b.
• In silico studies supported the in vitro findings, elucidating the inhibition mechanism and binding interactions.

Conclusions:

• The synthesized isoxazole-triazole conjugates represent a promising class of antibacterial agents.
• Compound 7b is a potent bactericidal agent with favorable pharmacokinetic properties.
• Further investigation into compound 7b is warranted for potential therapeutic applications against bacterial infections.