ABSTRACT
We are interested in new non-natural glycosides with sialic acid conjugates and their biological activities. We report the synthesis of eleven non-natural occurring glycosides, which are triterpene (glycyrrhetinic acid and its derivatives)-sialic acid conjugates, and their inhibitory activities against influenza virus sialidases and influenza virus multiplication in MDCK host cells. Deoxoglycyrrhetol-sialic acid conjugates (6d and 6e) and oleanolic acid-sialic acid conjugates (7d and 7e) showed strong inhibitory activities against three subtypes of influenza virus sialidases. These four compounds (6d, 6e, 7d and 7e) showed clear inhibition to influenza virus multiplication but not to MDCK host cell survival.
Subject(s)
Antiviral Agents/pharmacology , N-Acetylneuraminic Acid/pharmacology , Orthomyxoviridae/drug effects , Triterpenes/pharmacology , Animals , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Cell Survival/drug effects , Chickens , Dogs , Dose-Response Relationship, Drug , Madin Darby Canine Kidney Cells , Microbial Sensitivity Tests , Molecular Structure , N-Acetylneuraminic Acid/chemistry , Structure-Activity Relationship , Triterpenes/chemistryABSTRACT
A major hallmark of Alzheimer's disease is the cerebral accumulation and resulting cytotoxicity of amyloid-ß peptides, particularly Aß42. In this study, we used an MTT assay to investigate the inhibitory activity of biflavonoids 1-22 against Aß42 cytotoxicity in PC-12 cell cultures. Cytoprotective effects were observed for the following amentoflavone type biflavonoids: podocarpusflavone B 8, isoginkgetin 10, sciadopitysin 13, and kayaflavone 15. These biflavonoids exhibited strong activity in tested compounds, with EC50 values of 5.18, 10.77, 9.84, and 5.29 µM, respectively. Cell viability tests of PC-12 cells revealed that biflavonoids 13 and 15 had stronger inhibitory activities than apigenin 23 and (-)-epigallocatechin gallate 24.
Subject(s)
Amyloid beta-Peptides/toxicity , Biflavonoids/chemistry , Biflavonoids/pharmacology , Cell Survival/drug effects , Peptide Fragments/toxicity , Protective Agents/chemistry , Protective Agents/pharmacology , Animals , PC12 Cells , Rats , Structure-Activity RelationshipABSTRACT
Four novel benzo[j]fluoranthene derivatives, hypoxylonols C (3), D (4), E (5), and F (6), have been isolated from the mushroom Hypoxylon truncatum, together with two known benzo[j]fluoranthene derivatives, hypoxylonols A (1) and B (2). The structures were established by analysis of NMR spectroscopic data and X-ray diffraction data. Compounds 4 and 5 showed antiproliferative activity against HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical artery endothelial cells).
Subject(s)
Agaricales/chemistry , Fluorenes/isolation & purification , Fluorenes/chemistry , Fluorenes/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , X-Ray DiffractionABSTRACT
Three new diterpenes, myrocin D (1), libertellenone E (2), and libertellenone F (3), and a new isocoumarin, decarboxyhydroxycitrinone (4), were isolated from the marine fungus Arthrinium sacchari, together with three known compounds (5-7). The structures of 1-4 were elucidated from spectroscopic data (NMR, MS, IR), and the absolute configurations of 1-3 were determined by X-ray diffraction analysis. The antiangiogenic activity of these compounds was evaluated by measuring their antiproliferation effects on human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs). Compounds 4-7 showed inhibitory activity.
Subject(s)
Angiogenesis Inhibitors/isolation & purification , Ascomycota/chemistry , Diterpenes/isolation & purification , Isocoumarins/isolation & purification , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/pharmacology , Crystallography, X-Ray , Diterpenes/chemistry , Diterpenes/pharmacology , Endothelial Cells/drug effects , Humans , Isocoumarins/chemistry , Isocoumarins/pharmacology , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Umbilical Cord/cytology , Umbilical Cord/drug effectsABSTRACT
Here, we describe amentoflavone-type biflavonoids, which were isolated from natural sources and were found to inhibit beta-secretase (BACE-1). The structure-activity relationship was studied, and compounds 1-8, 10, 17, and 18 showed BACE-1 inhibitory activity. Among these compounds, 2,3-dihydroamentoflavone 17 and 2,3-dihydro-6-methylginkgetin 18 exhibited potent inhibitory effects with IC(50) values of 0.75 and 0.35 microM, respectively.
Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Biflavonoids/chemistry , Protease Inhibitors/chemistry , Amyloid Precursor Protein Secretases/metabolism , Biflavonoids/pharmacology , Protease Inhibitors/pharmacology , Structure-Activity RelationshipABSTRACT
Three novel p-terphenyl compounds, named boletopsins A (1), B (2), and C (3), and four known analogues (4-7) were isolated from fruiting bodies of the mushroom Boletopsis leucomelas. Compounds 1-7 were tested for KDR kinase inhibitory activity, and boletopsin C (3) was found to have an IC(50) value of 70.7 microM. Compound 3 also showed inhibition of proliferation of human umbilical vein endothelial cells, with an IC(50) value of 9.04 microM.
Subject(s)
Agaricales/chemistry , Terphenyl Compounds/isolation & purification , Terphenyl Compounds/pharmacology , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Endothelial Cells/drug effects , Fruiting Bodies, Fungal/chemistry , Humans , Inhibitory Concentration 50 , Japan , Molecular Structure , Terphenyl Compounds/chemistry , Umbilical Veins/cytology , Umbilical Veins/drug effectsABSTRACT
The aims of this study were to investigate the role of tyrosine kinase in intracellular signaling and to search for lead compounds with tyrosine kinase inhibitory activity from metabolites of marine-derived fungi. We initially prepared 400 extracts from 200 species of marine fungi and then subjected them to a tyrosine kinase screening assay using human umbilical vein endothelial cell lysate. Tyrosine kinase inhibitory activity was observed among certain metabolites of Hypocrea vinosa. We isolated one known compound, SC2051 (1), as well as two new compounds, hypochromins A (2) and B (3), which have a bis(naphtho-gamma-pyrone) skeleton. Compounds 1-3 showed tyrosine kinase inhibitory activity, with IC(50) values of 42.1, 58.7, and 18.0 microMu, respectively. Furthermore, compounds 1-3 exhibited inhibitory effects on proliferation, migration, and tubule formation.
Subject(s)
Angiogenesis Inhibitors/isolation & purification , Angiogenesis Inhibitors/pharmacology , Hypocrea/chemistry , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrones/isolation & purification , Pyrones/pharmacology , Angiogenesis Inhibitors/chemistry , Humans , Inhibitory Concentration 50 , Japan , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Pyrones/chemistry , Umbilical Veins/cytology , Umbilical Veins/drug effectsABSTRACT
Ginkgetin was found to inhibit the influenza virus sialidase. Ginkgetin-sialic acid conjugates showed a significant survival effect in the influenza-virus-infected mice.
