Topoisomerase i inhibitory compounds from the roots of paphiopedilum callosum

Abstract

Paphiopedilum callosum (Rchb.f.) Stein belongs to the Orchidaceae family. The phytochemistry and bioactivity of this plant have not been previously reported. In this study, the chromatographic separation of methanolic extract of P. callosum roots was bioassay-guided by a yeast cell-based assay. One new compound, 3′-hydroxy-2,6,5′-trimethoxystilbene (PC1) and five known compounds including 3′-hydroxy-2,5′-dimethoxystilbene (PC2), 3-methylethergalangin (PC3), galangin (PC4), 2,3′-dihydroxy-5,5′-dimethoxystilbene (PC5) and 2,3′-dihydroxy-5′-methoxystilbene (PC6) were isolated. The chemical structures of these isolated compounds were elucidated and identified on the basis of analysis spectroscopic (ESI-MS, NMR and IR), as well as comparison with those reported in the literature. Their topoisomerase I poison activity was examined by a yeast cell-based assay. The results indicated that all the compounds exerted inhibitory effect on the growth of yeast cells, suggesting their TopI poison activities. The cytotoxic activities on human cancer cell lines (MCF-7 and NCI-H187), were also evaluated. The compounds exhibited varying degrees of cytotoxicity on the representative cell lines. Topoisomerase I poison activity of compounds was confirmed by DNA-cleavage assay, using supercoiled DNA. The results suggested that compounds caused the DNA-TopI cleavage complex, characteristics of TopI poison, by forming the nicked DNA. Further detailed studies on the isolated compounds might be provided useful information for cancer drug development.