Microwave-assisted synthesis and in silico antibacterial evaluation of acridine derivatives

Acridines constitute an important class of nitrogen-containing heterocyclic compounds that have attracted considerable attention in medicinal chemistry because of their broad spectrum of biological activities, including antibacterial, anticancer, antioxidant, anticonvulsant, and antimalarial properties. In the present study, a series of novel acridine derivatives was synthesized through the microwave-assisted condensation of various β-enaminones with aromatic aldehydes under catalyst-free conditions. This green synthetic strategy afforded the target compounds in good to excellent yields within short reaction times under mild conditions, providing an efficient and environmentally friendly alternative to conventional methods. The synthesized compounds were characterized by spectroscopic techniques, including Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. Their antibacterial potential was subsequently investigated by in silico molecular docking against Bacillus anthracis dihydropteroate synthase (BaDHPS), a key enzyme involved in bacterial folate biosynthesis. Docking analysis revealed favorable binding affinities and demonstrated that the most active derivatives established hydrogen-bonding, hydrophobic, and π-interactions with essential amino acid residues within the catalytic pocket of BaDHPS. These interactions suggest a plausible mechanism for enzyme inhibition and highlight the potential of the synthesized acridine derivatives as promising antibacterial candidates. The combination of a green synthetic methodology and computational evaluation provides a valuable foundation for the future design and development of acridine-based antibacterial agents.