Antitumor Steroids

1st Edition - September 9, 1992
Author: R T Blickenstaff
Language: English
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 1 3 9 1 6 - 8

Antitumor Steroids examines the use of steroids, along with nonsteroidal antiestrogens and some benzo[a]carbazoles, in the treatment of cancer. It explains the mechanism by which… Read more

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Antitumor Steroids examines the use of steroids, along with nonsteroidal antiestrogens and some benzo[a]carbazoles, in the treatment of cancer. It explains the mechanism by which steroids and their receptors work together to affect their physiological functions in general and their antitumor activity in particular. It also describes the systematic screening of antitumor compounds isolated from natural sources. Organized into nine chapters, this book begins with an overview of the role of steroids in cancer treatment. It then discusses the estrogens, antiestrogens, and compounds (all containing an aromatic A-ring). The next chapters consider androgens, some antiandrogens, derivatives based on C-19 steroids, progestins and corticoids, bile acids, and compounds with a side-chain carboxyl group. The book explains the biogenesis and metabolism of androgens; the pharmacology of medroxyprogesterone acetate; the antitumor properties of naturally occurring corticosteroids; sterols and cucurbitacins; vitamin D and its metabolites; and cardenolides, bufadienolides, and withanolides. The book concludes with a chapter on bile acids, sapogenins and its analogs, and miscellaneous steroids. This book is a valuable resource for organic and medicinal chemists biochemists, and pharmacologists interested in the use of steroids in treating cancer.

Preface

1 The Role of Steroids in Cancer Treatment

1.1 Introduction

1.2 Steroid Receptors

1.3 Mechanisms of Antitumor Action

1.4 Antitumor Testing

1.5 Reviews

References

2 Estrogens, Antiestrogens, and Other Estrane Compounds

2.1 Introduction

2.2 Naturally Occurring C-18 Estrogens

2.3 Carbamates

2.4 Antiestrogens

2.4.1 Triphenylethylenes

2.4.2 Diphenyl Analogs of Diethylstilbestrol and Hexestrol

2.4.3 Diphenyl and Triphenyl Cytotoxic-Linked Estrogens

2.5 cis-Platinum(II) Complexes of Steroids

2.6 Esters of m-[Bis-(2'-chloroethyl)amino]benzoic Acid,

p-[Bis-(2' -chloroethyl)amino]phenylacetic Acid, and 4-{p-[Bis-(2'-chloroethyl)amino]phenyl]

butyric Acid

2.7 Nitrosoureas

2.8 Bis-(2-chloroethyl)amines and Aziridines

2.9 11- and 7-Substituted Estradiol Derivatives

2.10 Miscellaneous

2.10.1 Nitro, Amino, and Thiourea Derivatives

2.10.2 Epoxides

2.10.3 Tetracyclic Analogs (Aza-C-nor-D-homo Steroids)

2.10.4 ABD-Antiestrogens

2.10.5 Deoxyuridine, 5-Flurouricil, and Adenine Derivatives

2.10.6 Diethylstilbestrol and Hexestrol Derivatives

2.10.7 Cyclophosphamides

2.10.8 Deacetylvinblastine Conjugates

2.10.9 Intercalating Agents

2.10.10 Benzosteroids

2.10.11 Aza and Diaza Steroids

2.10.12 Radioligands

2.10.13 Ring-D Lactones

2.10.14 Polyestradiol Phosphate

2.10.15 17α-Mercapto-l,3,5(10)-Estratrien-3-ol

2.10.16 2-Methanesulfonoxyestrone

2.11 Summary

References

3 Androgens and Other Androstane Derivatives

3.1 Introduction

3.2 Biogenesis and Metabolism of Androgens

3.3 Antitumor Activities of Naturally Occurring C-19 Steroids

3.4 Aromatase Inhibitors

3.5 11β-Substituted Antiprogestins

3.6 5α-Reductase Inhibitors

3.7 Lactones

3.8 Esters of p-[Bis-(2'-chloroethyl)amino]phenylacetic Acid, 4-{p-[Bis-(2'-chloroethyl)amino]phenyl]butyric Acid, and

p-[Bis-(2'-chloroethyl)amino]phenoxyacetic Acid

3.9 Anabolic Compounds

3.10 Carbamates

3.11 Nitrosoureas

3.12 2-Chloroethylamines and Bis-(2-chloroethyl)amines

3.13 Aziridines

3.14 Miscellaneous

3.15 Summary

References

4 Progestins ans Other Pregnane Derivatives

4.1 Introduction

4.2 Biogenesis of Progesterone

4.3 Mechanism of Antitumor Action

4.4 Progesterone, Pregnenolone, 17α:-Hydroxyprogesterone and its Caproate, and Other Naturally Occurring C-20 Steroids

4.5 Medroxyprogesterone Acetate

4.5.1 Pharmacology

4.5.2 Breast Cancer

4.5.3 Medroxyprogesterone Acetate versus Tamoxifen

4.5.4 Medroxyprogesterone Acetate with Chemotherapy

4.5.5 Ovarian Cancer

4.5.6 Endometrial Cancer

4.5.7 Prostate Cancer

4.5.8 Renal Cancer

4.6 Megestrol Acetate

4.6.1 Pharmacology

4.6.2 Breast Cancer

4.6.3 Prostate Cancer

4.6.4 Renal Cell Carcinoma

4.6.5 Ovarian Cancer

4.6.6 Endometrial Cancer

4.7 Cyproterone Acetate

4.8 Nucleosides and Related Compounds

4.9 Aziridines

4.10 Bis-(2-chloroethyl)aminophenyl Compounds

4.11 Carbamates

4.12 Nitrosoureas

4.13 α-Methylene-γ-lactone

4.14 5α-Reductase Inhibitors

4.15 Summary

References

5 Corticoids

5.1 Naturally Occurring Corticosteroids

5.2 Antitumor Effects of Corticosteroids

5.3 Anti-Inflamatory Effects

5.4 Effect on the Immune System

5.5 Antiangiogenesis

5.6 Combination Therapy with Prednisone and Prednisolone

5.7 Prednimustine and Other Alkylating Agents

5.8 Nucleoside Conjugates

5.9 Miscellaneous

5.10 Management of Symptoms

5.11 Summary

References

6 Sterols and Cucurbitacins

6.1 Sterols

6.1.1 General Introduction

6.1.2 Biosynthesis of Sterols

6.1.3 Naturally Occurring Sterols and Their Simple Derivatives

6.1.4 Esters of p-[Bis-(2'-chloroethyl)amino]phenylacetic Acid and 4-{p-[Bis-(2'-chloroethyl)amino]phenyl} butyric Acid

6.1.5 N-(2-Chloroethyl)amines

6.1.6 Nitrosoureas

6.1.7 Muramyl Peptide

6.1.8 Sulfur and Selenium Compounds

6.1.9 Aziridines (Ethylene Imines)

6.1.10 Carbamates

6.1.11 α-Methylene Lactones

6.1.12 Miscellaneous

6.2 Cucurbitacins

6.3 Summary

References

7 Vitamin D

7.1 Introduction to Vitamin D and Its Metabolites

7.2 Metabolism of Vitamin D

7.3 Antitumor Effects of Calcitriol

7.4 Vitamin D Compounds Tested for Antitumor Activity in Vitro

7.4.1 Scope

7.4.2 Classification

7.4.3 Data

7.4.4 Calcitrol and Analogs Modified Only in the Side Chain

7.4.5 Analogs of Calcitriol or Side-Chain Modified Analogs Formed by Structural Changes in the Secosteroid Nucleus

7.4.6 Structure—Activity Relationships

7.4.7 Synthetic Strategies

7.5 In Vivo Testing of Antitumor Vitamin D Compounds and Future Prospects

References

8 Cardenolides, Bufadienoudes and Withanolides

8.1 Cardenolides

8.2 Bufadienolides

8.3 Withanolides

8.4 Summary

References

9 Bile Acids, Sapogenins, and Miscellaneous Steroids

9.1 Bile Acids

9.2 Sapogenins and Analogs

9.3 Miscellaneous Steroids

9.4 Summary

References

Appendix

Author Index

Subject Index