Anti-HBV and cytotoxic activities of pyranocoumarin derivatives.

Abstract 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 1.34 μM, 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.