Semisynthesis And Kappa-Opioid Receptor Activity Of Derivatives Of Columbin, A Furanolactone Diterpene
| Autor: | Rachel Saylor Crowley, Anil Yilmaz, Alexander M. Sherwood, Thomas E. Prisinzano |
|---|---|
| Přispěvatelé: | YILMAZ, ANIL |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist Ranunculus Tinospora medicine.drug_class Pharmaceutical Science Pharmacology Ligands 01 natural sciences Furanolactone Article Analytical Chemistry Diterpenes Clerodane 03 medical and health sciences chemistry.chemical_compound Lactones Structure-Activity Relationship Drug Discovery medicine Structure–activity relationship Animals Analgesics Molecular Structure 010405 organic chemistry Salvinorin Receptors Opioid kappa Organic Chemistry Semisynthesis Salvinorin A 0104 chemical sciences 030104 developmental biology Complementary and alternative medicine chemistry Opioid Africa Molecular Medicine Diterpene Diterpenes medicine.drug |
| Popis: | Columbin (1) is a furanolactone diterpene isolated from the roots of Jateorhiza and Tinospora species. These species generally grow in Asia and Africa and have been used in folk medicine for their apparent analgesic and antipyretic activities. Columbin (1) is of particular interest due to its structural similarity to the known kappa-opioid receptor (KOR) agonist salvinorin A. Given that the KOR is of interest in the study of many serious diseases, such as anxiety, depression, and drug addiction, obtaining natural or semisynthetic molecules with KOR activity recently has gained much interest. For this reason, in the present study, derivatives of 1 were designed and synthesized using known structure-activity relationships of salvinorin A at KORs. The structures of the columbin analogues prepared were elucidated by NMR spectroscopy and mass spectroscopy, and their KOR activity was investigated in vitro by inhibition of forskolin-induced cAMP accumulation. Slight improvements in KOR activity were observed in columbin derivatives over their parent compound. However, despite the structural similarities to salvinorin A, neither columbin (1) nor its derivatives were potent KOR ligands. This work represents not only the first evaluation of columbin (1) at the KOR but also one of the first works to explore synthetic strategies that are tolerated on the columbin core. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|