Andrographolide (Andro), the main active component of the herb Andrographis paniculata, has been used
for many years to treat a variety of diseases including bacterial and viral infections. Andro was recently
reported to act by inhibiting the bacterial quorum sensing system. We have synthesized several Andro
analogues and investigated their antibacterial activity and mechanism of action. The new compounds
were found to be much more potent than the parent Andro in inhibiting bacterial growth and quorum
sensing system. Compounds 5 and 7 significantly reduced virulence factor production. Compound 7
completely inhibited Pseudomonas aeruginosa (P. aeruginosa) biofilm formation, and exhibited synergistic
activity with conventional antibiotics. These findings suggest that compound 7 may be the basis for
future drug development to combat the unmet needs of virulence factor production, biofilm formation
and antibiotic resistance.