ABSTRACT
Two monoterpenoid indole alkaloid erchinines A (1) and B (2), possessing unique 1,4-diazepine fused with oxazolidine architecture and three hemiaminals, were isolated from Ervatamia chinensis. Their structures were elucidated on the basis of intensive spectroscopic analysis, and a plausible biosynthetic pathway from ibogaine was proposed. Both compounds exhibited significant antimicrobial activity against Trichophyton rubrum and Bacillus subtilis, and their activities were comparable to the first line antifungal drug griseofulvin and antibiotic cefotaxime.
Subject(s)
Apocynaceae , Anti-Infective Agents , Indole Alkaloids , Molecular Structure , Organic ChemicalsABSTRACT
Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz-enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90ß. At the molecular level, inactivation of HSP90 can mimic vibsanin B's effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90ß and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.
Subject(s)
Cell Movement/drug effects , Diterpenes/pharmacology , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , HSP90 Heat-Shock Proteins/metabolism , Leukocytes/drug effects , Leukocytes/immunology , Animals , Cell Line , Central Nervous System/drug effects , Central Nervous System/immunology , Central Nervous System/metabolism , Central Nervous System/pathology , Diterpenes/administration & dosage , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Humans , Leukocytes/metabolism , Mice , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Spinal Cord/drug effects , Spinal Cord/immunology , Spinal Cord/metabolism , Spinal Cord/pathology , ZebrafishABSTRACT
Investigation of the alkaloids from Myrioneuron faberi, a plant unique to China, gave four pairs of enantiomers (1-4). (±)-ß-Myrifabral A (1) and (±)-α-myrifabral A (2) formed an inseparable mixture of anomers (cluster A), as did (±)-ß-myrifabral B (3) and (±)-α-myrifabral B (4) (cluster B). Their structures were determined by X-ray diffraction and NMR analysis. Compounds 1-4 possessed novel cyclohexane-fused octahydroquinolizine skeletons and represent the first quinolizidine alkaloids from the genus Myrioneuron. The epimers of cluster A (1 and 2) were modified and separated. In vitro, clusters A and B and their derivatives inhibited replication of hepatitis C virus (HCV, IC50 0.9 to 4.7 µM) with cytotoxicity lower than that of telaprevir.
Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cyclohexanes/chemistry , Cyclohexanes/pharmacology , Hepacivirus/drug effects , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Quinolizines/chemistry , Quinolizines/pharmacology , Alkaloids/isolation & purification , Antiviral Agents/isolation & purification , Crystallography, X-Ray , Cyclohexanes/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Quinolizines/isolation & purification , StereoisomerismABSTRACT
A small focused library which comprised of l-AA lactone derivatives was built with a facile method. This reported method was optimized by modifying the acidity of the solvent. As a result, 12 l-AA lactones were synthesized. Among these lactones, lactones 8-12 were new compounds. The cytotoxicity of these synthetic compounds were investigated.
