Aloe emodin-conjugated sulfonyl hydrazones as novel type of antibacterial modulators against S. aureus 25923 through multifaceted synergistic effects

Aloe emodin-conjugated sulfonyl hydrazones were designed and synthesized as novel type of antibacterial modulators. Aloe emodin benzenesulfonyl hydrazone 5a (AEBH-5a) was preponderant for the treatment of S. aureus 25923 (MIC = 0.5 μg/mL) over norfloxacin and presented high selectivity between bacterial membranes and mammalian membranes. Especially, AEBH-5a could eliminate the formed biofilms and relieve the development of S. aureus 25923 resistance. The antibacterial mechanism of AEBH-5a from extracellularity to intracellularity illustrated that AEBH-5a could destroy bacterial membrane integrity, leading to the leakage of protein and nucleic acid. Besides, AEBH-5a could not only interact with DNA and induce oxidative stress but also inhibit lactate dehydrogenase (LDH) activity as well as render metabolic inactivation. In silico ADME studies prediction of AEBH-5a revealed a favorable bioavailability score and prominent drug-likeness profile. This research showed that the multifaceted synergistic effect initiated by aloe emodin-conjugated sulfonyl hydrazones is a reasonable and effective tactic to combat menacing bacterial infections.