Anti-HBV and cytotoxic activities of pyranocoumarin derivatives.
Four natural pyranocoumarins clausenidin (1), nordentatin (2), clausarin (3), and xanthoxyletin (4) were isolated from the medicinal plant Clausena excavata. Recently, we found that 1 and 2 suppressed hepatitis B virus surface antigen in HepA2 cells, and in addition, 1-3 showed cytotoxic activity against four human cancer cell lines (A549, MCF7, KB, and KB-VIN). To explore the SAR of 1-4, 17 pyranocoumarin analogues (5-21) were designed and synthesized. Among these analogues, 5 and 10 were the most potent against hepatitis B virus with EC(50) values of 1.14 and 1.34microM, respectively. The most interesting result in the cytotoxicity assay was the significant activity of 1, 5, and 6 against the multi-drug resistant cell line, KB-VIN, without activity against the KB cell line. These data suggest that these three compounds could be useful hits for developing MDR-inverse drugs.
Su
Chung-Ren
CR
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan.
Yeh
Sheau Farn
SF
Liu
Chih Miem
CM
Damu
Amooru G
AG
Kuo
Tsung-Hsiao
TH
Chiang
Po-Cheng
PC
Bastow
Kenneth F
KF
Lee
Kuo-Hsiung
KH
Wu
Tian-Shung
TS
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D054700:Clausena / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D010946:Plants, Medicinal / Q000737:chemistry; D039681:Pyranocoumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D039681:Pyranocoumarins