title: Synthesis and evaluation of antibacterial activities of andrographolide analogues.
abstract: 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.
authors.affiliation: Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Jiang
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhaoqi
authors.initials: Z
authors.lastname: Yang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Tian
authors.forename: Susan C
authors.initials: SC
authors.lastname: Wright
authors.forename: James W
authors.initials: JW
authors.lastname: Larrick
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D037521:Virulence Factors; C030419:andrographolide; D011710:Pyocyanine