19-Oxygenated Derivatives of Androst-4-ene-6,17-dione and Androst-5-ene-4,17-dione as Catalytic Probes for the Active Site of Aromatase
スポンサーリンク
概要
- 論文の詳細を見る
To gain insight into the binding manner of androst-4-ene-6,17-dione (4) and its 5-en-4-one analog 9,good competitive inhibitors of aromatase, in the active site of the enzyme, their 19-oxygenated derivatives were evaluated as inhibitors of human placental aromatase. The 19-hydroxy steroids 6,7,and 10 and the 19-oxo analogs 8 and 12 were much poorer competitive inhibitors than their corresponding parent 19-methyl steroids. Conversion of the 17-keto inhibitors, 4,6,and 10 to the 17β-ols 5,7,and 11,respectively, markedly decreased their affinity to the enzyme. The results suggest that steroids 4 and 9 would bind to the active site in a similar manner to that involved in the binding of the substrate androstenedione (1).
- 公益社団法人日本薬学会の論文
- 1999-10-15
著者
-
NUMAZAWA Mitsuteru
Tohoku College of Pharmacy
-
YAMADA Keiko
Tohoku Pharmaceutical University
-
KIDOKORO Kanae
Tohoku College of Pharmacy
-
Yamada Keiko
Tohoku College Of Pharmacy
関連論文
- Synthesis and GC-MS of 6-Alkylestradiols, Possible Aromatase Reaction Products of 6-Alkylandrostenediones
- Kinetic Analysis of Reversible Inhibition of 16α-Hydroxyandrostenedione Aromatization in Human Placental Microsomes by Suicide Substrates of Androstenedione Aromatization
- Gas Chromatography-Mass Spectrometric Determination of Activity of Human Placental Aromatase Using 16α-Hydroxyandrostenedione as a Substrate
- Synthesis of 19-Oxygenated 4β, 5β-Epoxy Derivatives of 16α-Hydroxyandrostenedione as Mechanistic and Catalytic Probes for Aromatase Reaction
- C(10)-C(19) Bond Cleavage Reaction of 19-Oxygenated Androst-4-ene-3,6-dione Steroids under Various Conditions
- Improved Synthesis and Molecular Modeling of 4β,19-Dihydroxyandrost-5-en-17-one, an Excellent Inhibitor of Aromatase
- Aromatization of 19-Oxygenated Androst-4-ene-3,6,17-triones with Human Placental Microsomes
- Synthesis and Biochemical Studies of 19-Oxygenated Derivatives of 6α- and 6β-Methylandrostenediones as Catalytic Probes for the Active Site of Aromatase
- 19-Oxygenation of C_-Steroids with an A, B-Ring Enone Structure, Competitive Inhibitors of Estrogen Biosynthesis, with Human Placental Aromatase
- Aromatase Inhibition by 4β, 5β-Epoxides of 16α-Hydroxyandrostenedione and Its 19-Oxygenated Analogs, Potential Precursors of Estriol Production in the Feto-Placental Unit
- Identification of 16α, 19-Dihydroxyandrostenedione in the Serum of Pregnant Women by Gas Chromatography-Mass Spectrometry
- Synthesis of Deuterium-Labeled Androst-5-ene-17β, 19-diol and Its 4-Ene Isomer as Internal Standards for the Determination of the 19-Oxygenation of Aromatase Inhibitors Using GC-MS
- Stereochemistry of NaBH_4 Reduction of a 19-Carbonyl Group of 3-Deoxy Androgens. Synthesis of [19S-^3H]- and [19R-^3H]-Labeled Aromatase Inhibitors Having a 19-Hydroxy Group
- DETERMINATION OF AROMATASE ACTIVITY INVOLVED IN THE FORMATION OF ESTRIOL WITH HUMAN PLACENTAL MICROSOMES AND ITS KINETIC PROPERTIES
- Formation of 17β-Alkoxy-16-keto Steroids by Reaction of 16α-Hydroxy-17-keto and 17β-Hydroxy-16-keto Steroids with Trimethylsilyl Iodide in the Presence of Alkyl Alcohols
- Structure-Activity Relationships of Estrogen Derivatives as Aromatase Inhibitors. Effects of Heterocyclic Substituents
- Mechanistic Studies of Deoxygenation of Steroidal Ring-D 16,17-Ketols with trimethylsilyl Iodide
- Deoxygenation of Steroidal Ring-D 16,17-Ketols with Trimethylsilyl Iodide
- Aromatase Inactivation by a Suicide Substrate, Androst-5-ene-4,7,17-trione : The 5β, 6β-Epoxy-19-oxo Derivative, as a Possible Reactive Electrophile Irreversibly Binding to the Active Site
- 19-Oxygenated Derivatives of Androst-4-ene-6,17-dione and Androst-5-ene-4,17-dione as Catalytic Probes for the Active Site of Aromatase
- Gas Chromatography-Mass Spectrometric Study of 19-Oxygenation of the Aromatase Inhibitor 19-Methylandrostenedione with Human Placental Microsomes(Analytical Biochemistry)
- Reduction of 1,4-Dien-3-one Steroids with LiAl^2H_4 or NaB^2H_4 : Stereospecific Deuterium-Labeling at the C-1α Position of a 4-En-3-one Steroid
- Studies of the Time-Dependent Inactivation of Aromatase by 4β, 5β-Epoxy-6-one and 5β, 6β-Epoxy-4-one Steroids under Various Conditions
- Synthesis and Biochemical Properties of 6-Bromoandrostenedione Derivatives with a 2,2-Dimethyl or 2-Methyl Group as Aromatase Inhibitors(Medicinal Chemistry)