Synthesis, Antimicrobial Evaluation, and Interaction of Emodin Alkyl Azoles with DNA and HSA

Abstract

Objective: This study aimed to overcome the growing antibiotic resistance. Moreover, the new series of emodin alkyl azoles were synthesized. Method: The novel emodin alkyl azoles were synthesized using commercial emodin and azoles by alkylation. The NMR and HRMS spectra were employed to confirm the structures of novel prepared compounds. The in vitro antibacterial and antifungal activities of the prepared emodin compounds were studied by the 96-well plate method. The binding behavior between emodin 4-nitro imidazole compound 3c and S. aureus DNA was researched using an ultraviolet-visible spectrophotometer. Furthermore, fluorescence spectrometry was used to explore the interaction with human serum albumin (HSA). Results: The in vitro antimicrobial results displayed that compound 3c gave relatively strong activities with MIC values of 4−16 μg/mL. Notably, this compound exhibited 2-fold more potent activity against S. aureus (MIC = 4 μg/mL) and E. coli (MIC = 8 μg/mL) strains than clinical drug Chloromycin (MIC = 8 and 16 μg/mL). The UV-vis absorption spectroscopy showed that 4-nitro imidazole emodin 3c could form the 3c-DNA complex by intercalating into S. aureus DNA, inhibiting antimicrobial activities. The simulation results displayed that the emodin 3c and DNA complex were formed by hydrogen bonds. The spectral experiment demonstrated that compound 3c could be transported by human serum albumin (HSA) via hydrogen bonds. The molecular simulation found that the hydroxyl group and the nitroimidazole ring of the emodin compound showed an important role in transportation behavior. Conclusion: This work may supply useful directions for the exploration of novel antimicrobial agents.