Synthesis and evaluation of antibacterial activities of andrographolide analogues.
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.
Jiang
Xiaojian
X
Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou, China.
Yu
Pei
P
Jiang
Jie
J
Zhang
Zaijun
Z
Wang
Zhongli
Z
Yang
Zhaoqi
Z
Tian
Zhiming
Z
Wright
Susan C
SC
Larrick
James W
JW
Wang
Yuqiang
Y
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D011710:Pyocyanine / Q000096:biosynthesis; D053038:Quorum Sensing / Q000187:drug effects; D037521:Virulence Factors / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D004224:Diterpenes; D037521:Virulence Factors; C030419:andrographolide; D011710:Pyocyanine