Tetrandrine Derivatives as Promising Antibacterial Agents

Abstract

This work reports on the antibacterial activity of two tetrandrine derivatives, with acridine (MAcT) and anthracene (MAnT) units, against Gram-positive and Gram-negative bacteria of clinical importance by the broth microdilution method as well as their antioxidant activity against ABTS •+ and DPPH •+ radicals. Unlike natural tetrandrine, its derivatives inhibited bacterial growth, showing selectivity against Staphylococcus aureus with notable activity of MAnT (MIC = 0.035 μg/mL); this compound also has good activity against the ABTS •+ radical (IC 50 = 4.59 μg/mL). Cell membrane integrity studies and reactive oxygen species (ROS) detection by fluorescent stains helped to understand possible mechanisms related to antibacterial activity, while electrophoretic mobility assays showed that the derivatives can bind to bacterial DNA plasmid. The results indicate that MAnT can induce a general state of oxidative stress in S. aureus and Escherichia coli, while MAcT induces an oxidative response in S. aureus. Complementary electrochemical studies were included.