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Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents
- Source :
- Bioorganic & Medicinal Chemistry. 25:5216-5237
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Estrogens play undisputedly important physiological roles, but lifetime exposure to estrogens has also been linked to the development of breast cancer. Moreover, imbalanced estrogen levels have been associated with various symptoms such as osteoporosis and menopausal disorders. For the improvement of such estrogen imbalances, estrogenic reagents with regulatory properties have shown promising potential. Herein, we report the construction of a 12-arylbenzoacridine library via a diversity-oriented strategy that furnished non-toxic estrogenic and anti-estrogenic agents. Derivatives with a hydroxy group at the molecular edge exhibit potent binding affinity to the estrogen receptor α (ERα) and ERβ (IC50 < μM), while binding to the estrogen-related receptor γ (ERRγ), i.e., an orphan nuclear receptor on which estrogens often trigger unfavorable events, was not observed. These findings offer valuable insights into 12-arylbenzoacridines as a novel platform for the development of selective estrogen-receptor modulators (SERMs).
- Subjects :
- medicine.drug_class
Clinical Biochemistry
Pharmaceutical Science
Estrogen receptor
Antineoplastic Agents
Pharmacology
010402 general chemistry
Binding, Competitive
01 natural sciences
Biochemistry
Structure-Activity Relationship
Estrogen-related receptor alpha
Drug Discovery
Tumor Cells, Cultured
medicine
Humans
Receptor
Molecular Biology
Estrogen receptor beta
Cell Proliferation
Dose-Response Relationship, Drug
Molecular Structure
010405 organic chemistry
Chemistry
Organic Chemistry
Estrogen Antagonists
Estrogens
0104 chemical sciences
Receptors, Estrogen
Nuclear receptor
Estrogen
Drug Design
MCF-7 Cells
Acridines
Molecular Medicine
Estrogen-related receptor gamma
Drug Screening Assays, Antitumor
Estrogen receptor alpha
hormones, hormone substitutes, and hormone antagonists
HeLa Cells
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....41e5ae9bbdacd1699b6aba945d8b410c