Synthesis and biological evaluation of a new class of quinazolinoneazoles as potential antimicrobial agents and their interactions with calf thymus DNA and human serum albumin

Abstract

A series of novel quinazolinone azoles were synthesized and characterized by NMR, IR, MS and HRMS spectra. Bioactive assays showed that some target compounds exhibited significant antimicrobial potency. Especially, nitroimidazole derivative 3a displayed comparable or even superior antibacterial efficacies (MIC = 0.03–0.05 μmol mL⁻¹) in contrast with norfloxacin (MIC = 0.01–0.05 μmol mL⁻¹) and chloromycin (MIC = 0.02–0.10 μmol mL⁻¹). The preliminary interactive investigations of compound 3a with calf thymus DNA by UV-vis spectroscopy revealed that compound 3a could bind to DNA to form compound 3a–DNA complex by an intercalative mode and further block DNA replication to exert powerful antibacterial and antifungal activities. Hydrogen bonds and van der Waals forces played important roles in the association of compound 3a–HSA.