Synthesis and Biological Evaluation of Carbocyclic Analogues ofPachastrissamine
| Autor: | Yongseok Kwon, Woo-Jung Kim, Sang Kook Lee, Hoon Bae, Jayoung Song, Sanghee Kim, Joo-Youn Lee, Geun-Hee Han |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Molecular model Stereochemistry Cell Survival sphingosine kinase inhibitor Sphingosine kinase Pharmaceutical Science Article chemistry.chemical_compound Structure-Activity Relationship Sphingosine Drug Discovery Structure–activity relationship Humans Enzyme Inhibitors Coloring Agents Pharmacology Toxicology and Pharmaceutics (miscellaneous) lcsh:QH301-705.5 biology Kinase Rhodamines jaspine B molecular modeling Sphingolipid Molecular Docking Simulation Phosphotransferases (Alcohol Group Acceptor) Sphingosine kinase 1 chemistry lcsh:Biology (General) Docking (molecular) biology.protein cytotoxicity carbocyclic analogue Drug Screening Assays Antitumor pachastrissamine Protein Binding |
| Zdroj: | MARINE DRUGS(13): 2 Marine Drugs, Vol 13, Iss 2, Pp 824-837 (2015) Marine Drugs Volume 13 Issue 2 Pages: 824-837 |
| Popis: | A series of carbocyclic analogues of naturally-occurring marine sphingolipid pachastrissamine were prepared and biologically evaluated. The analogues were efficiently synthesized via a tandem enyne/diene-ene metathesis reaction as a key step. We found that the analogue 4b exhibited comparable cytotoxicity and more potent inhibitory activity against sphingosine kinases, compared to pachastrissamine. Molecular modeling studies were conducted to provide more detailed insight into the binding mode of 4b in sphingosine kinase. In our docking model, pachastrissamine and 4b were able to effectively bind to the binding pocket of sphingosine kinase 1 as co-crystalized sphingosine. However, 4b showed a hydrophobic interaction with Phe192, which suggests that it contributes to its increased inhibitory activity against sphingosine kinase 1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|