17beta-Hydroxysteroid dehydrogenase (17beta-HSD) type 1 converts estrone to estradiol, a potent ligand for estrogen receptors. It represents an important target for the development of drugs for treatment of estrogen-dependent diseases. In the present study, we have examined the inhibitory activities of some flavonoids, their biosynthetic precursors (cinnamic acids and coumaric acid), and their derivatives. The proliferative activity of flavonoids on the T-47D estrogen-receptor-positive breast cancer cell line was also evaluated. Among 10 flavonoids, 7,4'-dihydroxyflavone, diosmetin, chrysoeriol, scutellarein, genkwanin and fisetin showed more than 70% inhibition of 17beta-HSD type 1 at 6microM. In a series of 18 derivatives of cinnamic acid, the best inhibitor was 4'-cyanophenyl 3,4-methylenedioxycinnamate, with more than 70% inhibition of 17beta-HSD type 1. None of flavonoids affected the proliferation of T-47D breast cancer cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.mce.2008.09.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent advances in the development of 17beta-hydroxysteroid dehydrogenase inhibitors.
Steroids
January 2025
Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec Research Center-Université Laval, Québec, QC G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada.
Article Synopsis
- The 17β-hydroxysteroid dehydrogenases (17β-HSDs) family has multiple isoforms that can convert steroids between their alcohol and carbonyl forms based on the cofactor available.
- These enzymes play crucial roles in regulating estrogens and androgens, making them promising targets for therapies against conditions like breast cancer, prostate cancer, and Alzheimer's disease.
- The article reviews recent developments in inhibitors targeting various isoforms, highlighting both traditional and new dual inhibitors, organized by type and research group for clarity.
Synthesis and characterization of targeted 17β-hydroxysteroid dehydrogenase type 7 inhibitors.
J Steroid Biochem Mol Biol
September 2024
Organic Synthesis Service, CHU de Québec Research Center-Université Laval, Québec, QC G1V 4G2, Canada; Endocrinology and Nephrology Unit, CHU de Québec Research Center-Université Laval, Québec, QC G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada. Electronic address:
Sex steroid hormones such as estrogen estradiol (E2) and androgen dihydrotestosterone (DHT) are involved in the development of hormone-dependent cancers. Blockade of 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7), a member of the short chain dehydrogenase/reductase superfamily, is thought to decrease E2 levels while increasing those of DHT. Therefore, its unique double action makes this enzyme as an interesting drug target for treatment of breast cancer.
View Article and Find Full Text PDFPhf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.
Biochem Biophys Res Commun
April 2024
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, 28116, Republic of Korea. Electronic address:
Article Synopsis
- PhD finger protein 7 (Phf7) is crucial for spermiogenesis and male fertility, as its absence leads to infertility and growth issues in mice.
- Phf7 knockout mice exhibit lower body weight, reduced bone density, and increased osteoclasts, indicating problems in bone remodeling.
- Lower testosterone levels and reduced expression of key steroidogenesis genes in Phf7 mice suggests that Phf7 deficiency hampers male hormone production, impacting overall bone health.
Quercetin Supplementation Alleviates Cadmium Induced Genotoxicity-Mediated Apoptosis in Caprine Testicular Cells.
Biol Trace Elem Res
October 2024
Reproductive Physiology Laboratory, Department of Zoology, Kurukshetra University, Kurukshetra, Haryana, 136119, India.
Being a common environmental pollutant, cadmium causes detrimental health effects, including testicular injury. Herein, we document the ameliorative potential of quercetin, a potent antioxidant, against cadmium-induced geno-cytotoxicity and steroidogenic toxicity in goat testicular tissue. Cadmium induced different comet types (Type 0 - Type 4), indicating the varying degree of DNA-damage in testicular cells.
View Article and Find Full Text PDFD-Aspartate Depletion Perturbs Steroidogenesis and Spermatogenesis in Mice.
Biomolecules
March 2023
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.
High levels of free D-aspartate (D-Asp) are present in vertebrate testis during post-natal development, coinciding with the onset of testosterone production, which suggests that this atypical amino acid might participate in the regulation of hormone biosynthesis. To elucidate the unknown role of D-Asp on testicular function, we investigated steroidogenesis and spermatogenesis in a one-month-old knockin mouse model with the constitutive depletion of D-Asp levels due to the targeted overexpression of D-aspartate oxidase (DDO), which catalyzes the deaminative oxidation of D-Asp to generate the corresponding α-keto acid, oxaloacetate, hydrogen peroxide, and ammonium ions. In the knockin mice, we found a dramatic reduction in testicular D-Asp levels, accompanied by a significant decrease in the serum testosterone levels and testicular 17β-HSD, the enzyme involved in testosterone biosynthesis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!