Synthesis and biological evaluation of novel isoxazole derivatives from acridone

Abstract The present study was carried out in an attempt to synthesize a new class of potential antibacterial agents. In this context, novel isoxazoles were synthesized and evaluated for their potential antibacterial behavior against four pathogenic bacterial strains. The synthesized compounds exhibited moderate‐to‐good antibacterial activity against these strains. The highest antibacterial activity was observed against the Escherichia coli strains, particularly for compounds 4a and 4e with phenyl and para ‐nitrophenyl groups on the isoxazole–acridone skeleton; they showed promising minimum inhibitory concentration values of 16.88 and 19.01 μg/ml, respectively, compared with the standard drug chloramphenicol (22.41 µg/ml). The synthesized compounds were subjected to in silico docking studies to understand the mode of their interactions with the DNA topoisomerase complex (PDB ID: 3FV5) of E. coli . The molecular docking results showed that compounds 4a – l occupy the active site of DNA topoisomerase (PDB ID: 3FV5), stabilized via hydrogen bonding and hydrophobic interactions, which may be the reason behind their interesting in vitro antibacterial activity.