ABSTRACT
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.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Croton/chemistry , Diterpenes, Kaurane/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Dimerization , Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/isolation & purification , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Molecular Structure , Structure-Activity RelationshipABSTRACT
AMP-activated protein kinase (AMPK) is a potential therapeutic target for the treatment of metabolic syndrome including obesity and type-2 diabetes. As part of an ongoing search for new AMPK activators from plants, this study found that the total extract of Myristica fragrans (nutmeg) activated the AMPK enzyme in differentiated C2C12 cells. As active constituents, seven 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans, tetrahydrofuroguaiacin B (1), saucernetindiol (2), verrucosin (3), nectandrin B (4), nectandrin A (5), fragransin C(1) (6), and galbacin (7) were isolated from this extract. Among the isolates, compounds 1, 4, and 5 at 5 microM produced strong AMPK stimulation in differentiated C2C12 cells. In addition, the preventive effect of a tetrahydrofuran mixture (THF) on weight gain in a diet-induced animal model was further examined. These results suggest that nutmeg and its active constituents can be used not only for the development of agents to treat obesity and possibly type-2 diabetes but may also be beneficial for other metabolic disorders.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Anti-Obesity Agents/pharmacology , Enzyme Activators/pharmacology , Myristica/chemistry , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/isolation & purification , Enzyme Activators/chemistry , Enzyme Activators/isolation & purification , Magnetic Resonance Spectroscopy , Mass SpectrometryABSTRACT
Two new diterpenoids, crotonkinensins A (1) and B (2), were isolated from the leaves of the Vietnamese endemic medicinal plant Croton tonkinensis. Their structures were determined to be 7alpha,10alpha-epoxy-14beta-hydroxygrayanane-1(5),16(17)-dien-2,15-dione (1) and 7alpha,10alpha-epoxy-14beta-hydroxygrayanane-1(2),16(17)-dien-15-one (2) by spectroscopic analysis. Compounds 1 and 2 showed strong anti-inflammatory effects on the LPS-induced COX-2 promoter activity and COX-2 expression in Raw 264.7 cells.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Croton/chemistry , Diterpenes/isolation & purification , Diterpenes/pharmacology , Plants, Medicinal/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase 2/drug effects , Cyclooxygenase 2/genetics , Diterpenes/chemistry , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Mice , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Leaves/chemistry , Stereoisomerism , VietnamABSTRACT
Bioassay-guided fractionation of the EtOAc extract of the stem bark of Erythrina abyssinica (Leguminosae) resulted in the isolation of three new (1-3), along with 12 known (4-15) pterocarpan derivatives. Their chemical structures were determined by physicochemical and spectroscopic data analysis (IR, UV, [alpha](D), CD, 1D and 2D NMR, and MS data). All the isolates were evaluated for their inhibitory effects on protein tyrosine phosphatase-1B (PTP1B), as well as their growth inhibition on MCF7, tamoxifen-resistant MCF7 (MCF7/TAMR), adriamycin-resistant MCF7 (MCF7/ADR) and MDA-MB-231 breast cancer cell lines. Compounds which exhibited PTP1B inhibitory activity (IC(50) values ranging from 4.2+/-0.2 to 19.3+/-0.3 microM) showed strong cytotoxic activity (IC(50) values from 5.6+/-0.7 to 28.0+/-0.2 microM). Our data suggested that pterocarpans could be considered as new anticancer materials by PTP1B inhibition.
