Abstract
Estrogens are known to be an important factor in the development of estrogen-sensitive diseases. Among the enzymes involved in the biosynthesis of steroid hormones, 17β-hydroxysteroid dehydrogenase type 12 (17β-HSD12) is responsible for the reduction of estrone (E1) to estradiol (E2), this later revealed to stimulate the proliferation of estrogensensitive cells. To better understand the role of 17β-HSD12 and to better control the formation of E2 in a therapeutic perspective, we concentrated our work on synthesizing inhibitors. Knowing that a side chain at position 17α and the absence of any functional group at position 3 of E2 are important for inhibitory activity, we generated two series of 17α- amido-3-desoxyestradiol derivatives and measured their potential as inhibitors of 17β-HSD12. Parallel liquid-phase organic synthesis was used to prepare library A (36 compounds), while library B (19 compounds) was generated by direct carbonylation using high density microwave irradiation. The inhibitory results have shown that compounds from library B produced promising inhibition of 17β-HSD12, unlike compounds from library A. Indeed, seven compounds in library B inhibited the enzyme activity (transformation of E1 to E2) by 41-57% and 69-74% at 1 and 10 μM, respectively.
Keywords: 17βHydroxysteroid dehydrogenase, enzyme, inhibitor, steroid, estrone, cancer, chemical synthesis, amination, amidation, estrogens
Current Enzyme Inhibition
Title: Synthesis and Evaluation of Amido-Deoxyestradiol Derivatives as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 12
Volume: 7 Issue: 3
Author(s): Siham Farhane, Michelle-Audrey Fournier and Donald Poirier
Affiliation:
Keywords: 17βHydroxysteroid dehydrogenase, enzyme, inhibitor, steroid, estrone, cancer, chemical synthesis, amination, amidation, estrogens
Abstract: Estrogens are known to be an important factor in the development of estrogen-sensitive diseases. Among the enzymes involved in the biosynthesis of steroid hormones, 17β-hydroxysteroid dehydrogenase type 12 (17β-HSD12) is responsible for the reduction of estrone (E1) to estradiol (E2), this later revealed to stimulate the proliferation of estrogensensitive cells. To better understand the role of 17β-HSD12 and to better control the formation of E2 in a therapeutic perspective, we concentrated our work on synthesizing inhibitors. Knowing that a side chain at position 17α and the absence of any functional group at position 3 of E2 are important for inhibitory activity, we generated two series of 17α- amido-3-desoxyestradiol derivatives and measured their potential as inhibitors of 17β-HSD12. Parallel liquid-phase organic synthesis was used to prepare library A (36 compounds), while library B (19 compounds) was generated by direct carbonylation using high density microwave irradiation. The inhibitory results have shown that compounds from library B produced promising inhibition of 17β-HSD12, unlike compounds from library A. Indeed, seven compounds in library B inhibited the enzyme activity (transformation of E1 to E2) by 41-57% and 69-74% at 1 and 10 μM, respectively.
Export Options
About this article
Cite this article as:
Farhane Siham, Fournier Michelle-Audrey and Poirier Donald, Synthesis and Evaluation of Amido-Deoxyestradiol Derivatives as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 12, Current Enzyme Inhibition 2011; 7 (3) . https://dx.doi.org/10.2174/157340811798807614
DOI https://dx.doi.org/10.2174/157340811798807614 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Perspectives of Protein Kinase C (PKC) Inhibitors as Anti-Cancer Agents
Mini-Reviews in Medicinal Chemistry Strategies of Engineering Nanoparticles for Treating Neurodegenerative Disorders
Current Drug Metabolism Proteomics Using Mammospheres as a Model System to Identify Proteins Deregulated in Breast Cancer Stem Cells
Current Molecular Medicine Flavonoids in Neurodegeneration: Limitations and Strategies to Cross CNS Barriers
Current Medicinal Chemistry Glucuronides in Anti-Cancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Advances in the Molecular Detection of ABC Transporters Involved in Multidrug Resistance in Cancer
Current Pharmaceutical Biotechnology Micropropagation: A Tool for the Production of High Quality Plant-based Medicines
Current Pharmaceutical Biotechnology Advances in α(v)β(3) Integrin-Targeting Cancer Therapy and Imaging with Radiolabeled RGD Peptides
Current Radiopharmaceuticals CDK12 Promotes Breast Cancer Progression and Maintains Stemness by Activating c-myc/β -catenin Signaling
Current Cancer Drug Targets Computational Methods to Predict Drug Safety
Current Computer-Aided Drug Design Comparison of the Growth Curves of Cancer Cells and Cancer Stem Cells
Current Stem Cell Research & Therapy Endocrine Therapy for Advanced Breast Cancer: Beyond Tamoxifen and Aromatase Inhibitors
Current Cancer Therapy Reviews Raman Spectroscopy-based Metabonomics of HIV-infected Sera Detects Amino Acid and Glutathione Changes
Current Metabolomics MicroRNAs Regulate the Epithelial to Mesenchymal Transition (EMT) in Cancer Progression
MicroRNA Prediction of the Estrogen Receptor Binding Affinity for both hER<sub>α</sub> and hER<sub>β</sub> by QSAR Approaches
Letters in Drug Design & Discovery Future Prospects for Old Chemotherapeutic Drugs in the Target-Specific Era; Pharmaceutics, Combinations, Co-Drugs and Prodrugs with Melphalan as an Example
Letters in Drug Design & Discovery PI3K/AKT/mTOR Inhibitors In Ovarian Cancer
Current Medicinal Chemistry Treatment Outcome of Three Female Adolescents with Borderline Personality Disorder
Adolescent Psychiatry Recent Development of CB2 Selective and Peripheral CB1/CB2 Cannabinoid Receptor Ligands
Current Medicinal Chemistry Recent Progress on Tumor Missile Therapy and Tumor Vascular Targeting Therapy as a New Approach
Current Vascular Pharmacology