ABSTRACT
The emergence of the H1N1 swine flu pandemic has the possibility to develop the occurrence of disaster- or drug-resistant viruses by additional reassortments in novel influenza A virus. In the course of an anti-influenza screening program for natural products, 10 xanthone derivatives (1-10) were isolated by bioassay-guided fractionation from the EtOAc-soluble extract of Polygala karensium. Compounds 1, 3, 5, 7, and 9 with a hydroxy group at C-1 showed strong inhibitory effects on neuraminidases from various influenza viral strains, H1N1, H9N2, novel H1N1 (WT), and oseltamivir-resistant novel H1N1 (H274Y) expressed in 293T cells. In addition, these compounds reduced the cytopathic effect of H1N1 swine influenza virus in MDCK cells. Our results suggest that xanthones from P. karensium may be useful in the prevention and treatment of disease by influenza viruses.
Subject(s)
Antiviral Agents/chemistry , Enzyme Inhibitors/chemistry , Influenza A virus/enzymology , Neuraminidase/antagonists & inhibitors , Polygala/chemistry , Xanthones/chemistry , Animals , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Cell Line , Dogs , Drug Resistance, Viral , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , HEK293 Cells , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H1N1 Subtype/enzymology , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H9N2 Subtype/drug effects , Influenza A Virus, H9N2 Subtype/enzymology , Influenza A virus/drug effects , Kinetics , Mutation , Neuraminidase/metabolism , Oseltamivir/pharmacology , Structure-Activity Relationship , Xanthones/isolation & purification , Xanthones/pharmacologyABSTRACT
Breast cancer is the most common malignant tumor in women these days accounting for approximately 24% of all cancer. During our screening program searching for cytotoxic materials from natural products, two new symmetric dimers of ent-kaurane diterpenoid, crotonkinensins C (1) and D (2), with connectivity at C-17 were isolated from the leaves of the Vietnamese endemic medicinal plant Croton tonkinensis. Their structures were determined on the basis of physicochemical and spectroscopic data. Compound 2 showed a potent cytotoxic activity against MCF-7, tamoxifen-resistant MCF-7 (MCF-7/TAMR), adriamycin-resistant MCF-7 (MCF-7/ADR), and MDA-MB-231 breast cancer cell lines.
