Synthesis and evaluation of antibacterial activities of andrographolide analogues

• Published in: European journal of medicinal chemistry Vol. 44; no. 7; pp. 2936 - 2943
• Main Authors: Jiang, Xiaojian, Yu, Pei, Jiang, Jie, Zhang, Zaijun, Wang, Zhongli, Yang, Zhaoqi, Tian, Zhiming, Wright, Susan C., Larrick, James W., Wang, Yuqiang
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.07.2009; Elsevier
• Subjects: Andrographolide; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria; Bacteria - cytology; Bacteria - drug effects; Bacteria - metabolism; Biofilm; Biological and medical sciences; Cell Proliferation - drug effects; Chemistry, Medicinal; Diterpenes - chemical synthesis; Diterpenes - chemistry; Diterpenes - pharmacology; Drug Design; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Pyocyanine - biosynthesis; Quorum sensing; Quorum Sensing - drug effects; Science & Technology; Virulence Factors - biosynthesis; Biofilm; Bacteria; Quorum sensing; Andrographolide; KAN-JANG; PSEUDOMONAS-AERUGINOSA LASI; COMMON COLDS; KAPPA-B; BACTERIAL BIOFILMS; LIPOIC ACID; DOUBLE-BLIND; CYSTIC-FIBROSIS; PANICULATA; EXPRESSION; Pseudomonadales; Five membered ring; Cell cell interaction; Oxygen heterocycle; Signal transduction; Organic disulfide; Structure activity relation; Bicyclic compound; Pseudomonadaceae; Pseudomonas aeruginosa; Secondary alcohol; Labdane derivatives; Chemical synthesis; Acylate; Terpenoid; Microorganism growth; Lactone; In vitro; Primary alcohol; Sulfur heterocycle; Diterpene; Inhibitor; Antibacterial agent
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2008.12.014

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. [Display omitted]