Depsides isolated from the Sri Lankan lichenParmotremasp. exhibit selective Plk1 inhibitory activity
| Autor: | Maya P. Singh, Selvaluxmy Kathirgamanathar, Leonard A. McDonald, Richard Harrison, Frank Loganzo, David E. Williams, Jenny Togias, Veranja Karunaratne, Raymond J. Andersen, Lauren Whitney |
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| Rok vydání: | 2011 |
| Předmět: |
Lichens
Molecular Sequence Data Pharmaceutical Science Cell Cycle Proteins Parmotrema Context (language use) Protein Serine-Threonine Kinases Depsides chemistry.chemical_compound Ascomycota Proto-Oncogene Proteins Drug Discovery Parmeliaceae Humans Amino Acid Sequence Protein Kinase Inhibitors Sri Lanka Pharmacology chemistry.chemical_classification Natural product biology General Medicine biology.organism_classification In vitro Enzyme Complementary and alternative medicine chemistry Biochemistry Molecular Medicine Depside |
| Zdroj: | Pharmaceutical Biology. 49:296-301 |
| ISSN: | 1744-5116 1388-0209 |
| DOI: | 10.3109/13880209.2010.517540 |
| Popis: | Mitotic kinase enzymes regulate critical stages of mitosis and are amenable to pharmacological inhibition. Since natural products have been a rich source of antimitotic inhibitors, we postulated that natural products would also provide effective inhibitors of mitotic kinases.To explore unique marine and terrestrial natural product sources for new anticancer drug leads, we screened our natural product extract library for polo-like kinase-1 (Plk1) kinase inhibitors.Extracts of the lichen Parmotrema sp. (Parmeliaceae) exhibited in vitro inhibitory activity. Bioassay-guided fractionation of the Parmotrema sp. extract led to the isolation of depside inhibitors.A new depside 1 has been isolated from the Sri Lankan lichen Parmotrema sp. along with the known metabolites 2 (β-collatolic acid) and 3 (β-alectoronic acid). The structure of depside 1 was elucidated by spectroscopic analysis. The three depsides 1-3 exhibited moderate inhibition of purified recombinant Plk1 kinase with IC₅₀ of 2.8, 0.7, and 1.7 µM, respectively, at 1 µM ATP. Inhibitory activity was also observed at high concentrations of ATP, suggesting the potential for activity in a cellular environment. The depsides were also tested against a panel of 23 other recombinant kinases and were found to possess up to 30-fold selectivity toward Plk1.These data suggest that the depsides 1-3 may serve as core structures that can be further explored as potential inhibitors of Plk1 and other kinases. |
| Databáze: | OpenAIRE |
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