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7-Substituted-melatonin and 7-substituted-1-methylmelatonin analogues: effect of substituents on potency and binding affinity
- Source :
- Bioorganicmedicinal chemistry. 15(13)
- Publication Year :
- 2007
-
Abstract
- A series of 7-substituted melatonin and 1-methylmelatonin analogues were prepared and tested against human and amphibian melatonin receptors. 7-Substituents reduced the agonist potency of all the analogues in the Xenopus laevis melanophore assay, 7-bromomelatonin (5d) and N-butanoyl 7-bromo-5-methoxytryptamine (5f) being the most active compounds, but both were 42-fold less potent than melatonin (1). Whereas all the analogues bind with lower affinity at the human MT(1) receptor than melatonin, 5d, 5f and N-propanoyl 7-bromo-5-methoxytryptamine (5e) show a similar binding affinity to melatonin at the MT(2) receptor and consequently show some MT(2) selectivity. These results suggest that the receptor pocket around C-7 favours binding by an electronegative group, suggesting an electropositive region in this area of the receptor.
- Subjects :
- Agonist
medicine.drug_class
Stereochemistry
Clinical Biochemistry
Xenopus
Pharmaceutical Science
Biochemistry
Chemical synthesis
Antioxidants
Cell Line
Melatonin
Structure-Activity Relationship
Xenopus laevis
Drug Discovery
medicine
Structure–activity relationship
Potency
Animals
Humans
Receptor
Molecular Biology
biology
Chemistry
Receptor, Melatonin, MT2
Receptor, Melatonin, MT1
Organic Chemistry
biology.organism_classification
In vitro
Recombinant Proteins
Molecular Medicine
medicine.drug
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 15
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry
- Accession number :
- edsair.doi.dedup.....8e9798c3e9f0df1f011217ab7ce5c2ed