Synthesis, structure–activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 10; pp. 2353 - 2359
• Main Authors: Chen, Hao, Ma, Yun-Bao, Huang, Xiao-Yan, Geng, Chang-An, Zhao, Yong, Wang, Li-Jun, Guo, Rui-Hua, Liang, Wen-Juan, Zhang, Xue-Mei, Chen, Ji-Jun
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.05.2014; Elsevier
• Subjects: Andrographis paniculata; Anti-HBV activity; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological Products; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dehydroandrographolide and andrographolide derivatives; Diterpenes - chemical synthesis; Diterpenes - chemistry; Diterpenes - pharmacology; DNA Replication - drug effects; DNA, Viral - biosynthesis; DNA, Viral - genetics; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B virus - physiology; Life Sciences & Biomedicine; Octanol–water partition coefficients; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; Structure–activity relationships; Virus Replication - drug effects; Dehydroandrographolide and andrographolide derivatives; Anti-HBV activity; Octanol–water partition coefficients; Structure–activity relationships; Dehydroandrographolide and; DESIGN; PARTITION-COEFFICIENTS; VIVO; ANALOGS; DRUG DISCOVERY; Octanol-water partition coefficients; Structure-activity relationships; IN-VITRO; andrographolide derivatives; INHIBITORS; CONSTITUENTS

Dehydroandrographolide and andrographolide, two natural diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC50 values of 22.58 and 54.07μM and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide...