Evaluation of Synthesized Ester or Amide Coumarin Derivatives on Aromatase Inhibitory Activity
| Autor: | Yuki Yamaguchi, Naozumi Nishizono, Kazuaki Oda |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Drug
Stereochemistry medicine.drug_class media_common.quotation_subject Substituent Pharmaceutical Science Structure-Activity Relationship chemistry.chemical_compound Drug Development Coumarins Amide medicine heterocyclic compounds Aromatase media_common Pharmacology Aromatase inhibitor biology Aromatase Inhibitors Active site Esters General Medicine Coumarin Amides chemistry biology.protein Aminoglutethimide medicine.drug |
| Zdroj: | Biological and Pharmaceutical Bulletin. 43:1179-1187 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b20-00035 |
| Popis: | Aromatase inhibitors are effective for the treatment of diseases such as breast cancer, which has led to an increase in their demand. However, only a limited number of aromatase inhibitor drugs are currently being marketed. In addition, considering the important aspect of drug resistance, the development of newer drug types is required. We have been developing inhibitors with backbone structures that differ from existing aromatase inhibitors. In this regard, we previously reported that diethylaminocoumarin dimers and thiazolyl coumarin derivatives possess strong aromatase inhibiting capabilities. In this study, we further examined the structure-activity relationships of coumarin derivatives synthesized from thiazolyl coumarin derivatives and their aromatase inhibiting capabilities. Consequently, amide coumarin N-benzhydryl-7-(diethylamino)-2-oxo-2H-chromene-3-carboxamide (IC50 values 4.5 µM) is inhibitor of aromatase. This inhibitor was found to be comparable aromatase inhibitory activity to the 1st generation aromatase inhibitor aminoglutethimide (3.2 µM). Substitution of the amide group on the amide coumarin derivative affects the aromatase inhibiting activity. Our findings suggest that the structure of each substituent changes the orientation of the compound in the active site of aromatase, thus creating a difference in their activities. |
| Databáze: | OpenAIRE |
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