Advances in Anticancer Agents in Medicinal Chemistry: Volume 2 E-Book

• Herausgeber: Bentham Science Publishers
• Kategorie: Fachliteratur
• Serie: Advances in Anticancer Agents in Medicinal Chemistry
• Sprache: Englisch

Seitenzahl: 699

Veröffentlichungsjahr: 2013

Beschreibung

Advances in Anticancer Agents in Medicinal Chemistry is an exciting eBook series comprising a selection of updated articles previously published in the peer-reviewed journal Anti-Cancer Agents in Medicinal Chemistry. The second Volume of this eBook series gathers updated reviews on several classes of molecules exhibiting anticarcinogenic potential as well as some important targets for the development of novel anticancer drugs.
Featured Anti-cancer molecules:
-Marine macrolides and their biological targets
-Organometallic supramolecular complexes including gold-based anticancer agents,
anti-cancer vaccines
-glyconanoparticles,
-isatin-based compounds,
-tripentone families of potential anticancer drugs
Drug targets in this volume include:
-selective estrogen receptor modulators,
-leukemia stem cells,
-glioblastoma cell migratory mechanisms
-Tyrosyl-DNA phosphodiesterase 1
Advances in Anticancer Agents in Medicinal Chemistry will be of particular interest to readers interested in anticancer drug therapy as the series provides relevant reviews written by experts in this important field.

Leseprobe

Table of Contents

Welcome

Table of Contents

Title

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FOREWORD

PREFACE

Marine Macrolides: Blue Biotechnology Against Cancer

Abstract

1.. INTRODUCTION

2.. MACROLIDES TARGETING CYTOSKELETON

2.1.. Macrolides Targeting Actin

2.2.. Macrolides Targeting Microtubules

2.3.. Macrolides Targeting Intermediate Filaments

3.. MACROLIDES TARGETING VACUOLAR TYPE (H+)-ATPASES

4.. MACROLIDES TARGETING RIBOSOMES

5.. PERSPECTIVES

Conflict of interest

ACKNOWLEDGEMENTS

Disclosure

REFERENCES

Recent Developments in Organometallic Supramolecular Complexes as Anticancer Drugs

Abstract

1.. INTRODUCTION

2.. TRANSITION METAL SUPRaMOLECULar ComplexES AS ANTICANCER AGENTS

2.1.. Noble Metal-Based Supramolecular Complexes as Anticancer Agents

2.1.1.. Platinum-Based Supramolecular Complexes as Anticancer Agents

2.1.2.. Palladium-Based Supramolecular Complexes as Anticancer Agents

2.1.3.. Gold -Based Supramolecular Complexes as Anticancer Agents

2.1.4.. Silver-Based Supramolecular Complexes as Anticancer Agents

2.1.5.. Ruthenium-Based Supramolecular Complexes as Anticancer Agents

2.1.6.. Rhodium-Based Supramolecular Complexes as Anticancer Agents

2.1.7.. Osmium-Based Supramolecular Complexes as Anticancer Agents

2.2.. Non-Noble Metal-Based Supramolecular Complexes as Anticancer Agents

2.2.1.. Titanium-Based Supramolecular Complexes as Anticancer Agents

2.2.2.. Vanadium-Based Supramolecular Complexes as Anticancer Agents

2.2.3.. Chromiun-Based Supramolecular Complexes as Anticancer Agents

2.2.4.. Manganese-Based Supramolecular Complexes as Anticancer Agents

2.2.5.. Iron-Based Supramolecular Complexes as Anticancer Agents

2.2.6.. Cobalt-Based Supramolecular Complexes as Anticancer Agents

2.2.7.. Nickel-Based Supramolecular Complexes as Anticancer Agents

2.2.8.. Copper-Based Supramolecular Complexes as Anticancer Agents

2.2.9.. Zinc-Based Supramolecular Complexes as Anticancer Agents

2.2.10.. Rhenium-Based Supramolecular Complexes as Anticancer Agents

2.3.. Lanthanide Series-Based Supramolecular Complexes as Anticancer Agents

3.. Non-Transition Metal Supramolecular Complexes as Anticancer Agents

3.1.. Gallium-Based Supramolecular Complexes as Anticancer Agents

3.2.. Organotin-Based Supramolecular Complexes as Anticancer Agents

4.. CONCLUSIONS AND OUTLOOKS

CONFLICT OF INTEREST

ACKNOWLEDGEMENTs

DISCLOSURE

REFERENCES

Perspective Gold(III)-Dithiocarbamato Anticancer Therapeutics: Learning from the Past, Moving to the Future

Abstract

INTRODUCTION

WHY DITHIOCARBAMATES?

ONCE UPON A TIME: “FIRST GENERATION” GOLD-DITHIOCAR-BAMATO ANTICANCER AGENTS

In Vitro Cytotoxic Activity

Solution Chemistry and DNA Binding Affinity

Inhibition of the Selenoenzyme Thioredoxin Reductase

An Intriguing Unexpected Surprise: Proteasome Inhibition

In Vivo Anticancer Activity

In Vivo Nephrotoxicity Studies

“SECOND GENERATION” GOLD-DITHIOCARBAMATO ANTICANCER AGENTS: TOWARD A TARGETED CHEMOTHERAPY?

Background: the “Trojan Horse”

Designing Strategy and Preliminary Results

CONCLUDING REMARKS

DISCLOSURE

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

REFERENCES

Toward Anticancer Therapeutics Based on Glycidic Structures

Abstract

1.. HISTORICAL INTRODUCTION

2.. CARBOHYDRATE-BASED ANTICANCER VACCINES: GENERAL CONSIDERATIONS

3.. SYNTHETIC STRATEGIES TOWARDS GLYCOCONJUGATES

3.1.. Strategies for the Construction of the Oligosaccharidic Chain

3.2.. Glycosidic Bond Formation Between the Oligosaccharide and the Amino Acid/Peptide Moieties

3.3.. Peptide/Glycopeptide Fragments Ligation

3.4.. Convergent Assembly

3.5.. Recombinant Methods

4.. GLYCOCONJUGATES AS ANTICANCER THERAPY

4.1.. Monovalent Constructs

Covalent Conjugate Ganglioside Vaccines

4.1.1.. Chemically Modified Glycan Structure in Glycoconjugates

4.2.. Monovalent Clustered Constructs

4.2.1.. Tn-Pam3CS Conjugates

4.2.2.. Multiple Antigen Glycopeptides (MAG) Presenting the Tn Epitope

4.2.3.. Other Tn Epitope Containing Constructs

4.3.. Multivalent Constructs

4.4.. Nanotechnology for Cancer Therapy

5.. CONCLUSION AND PERSPECTIVES

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

Disclosure

references

Recent Highlights in the Development of Isatin-Based Anticancer Agents

Abstract

1.. INTRODUCTION

2.. CYTOTOXIC AND ANTICANCER ACTIVITIES OF ISATIN DERIVATIVES

2.1.. Mono-, Di- and Tri-Substituted Aromatic Isatin Derivatives

2.2.. N-Alkyl Substituted Isatin Derivatives

2.3.. C2-Substituted Isatin Derivatives

2.4.. C3-Substituted Isatin Derivatives

2.4.1.. 3-Arylidene Derivatives

2.4.2.. Hydrazones and Imines

2.4.3.. Metal Complexes

2.4.4.. Isoindigo and Derivatives

2.4.5.. Miscellaneous

2.5.. Isatin-Based Conjugates

2.5.1.. Dual Action/Hybrid Agents

2.5.2.. Selectively Deliverable Conjugates

2.6.. Isatins in Combination Therapy

3.. CONCLUSIONS

ABBREVIATIONS1

Conflict of interest

ACKNOWLEDGEMENTs

Disclosure

REFERENCES

Tripentones: A Promising Series of Potent Anti-Cancer Agents

Abstract

Introduction

Synthesis of the tripentone system

Miscellaneous Route

Synthesis of heterocyclic tripentones

Biological properties of tripentones and SAR

Development of MR 22388 as a lead compound

Conclusion

CONFLICT OF INTEREST

ACKNOWLEDGEMENTs

DISCLOSURE

REFERENCES

Selective Estrogen Receptor Modulators as Treatments and Preventives of Breast Cancer

Abstract

1.. INTRODUCTION

2.. MECHANISM OF ESTROGEN ACTION

2.1.. Structure and Function of ER

2.2.. Co-Regulators

2.2.1.. Co-Activators

2.2.2.. Co-Repressors

3.. DRUG RESISTANCE TO SERMS

3.1.. Metabolic Resistance

3.2.. Intrinsic Resistance

3.3.. Acquired Resistance

4.. NEW SERMS

4.1.. Tamoxifen-Like SERMs

4.1.1.. Toremifene (Fareston)

4.1.2.. Ospemifene (Deaminohydroxytoremifene, FC-1271a)

4.1.3.. GW5638 (DPC974) and GW7604

4.2.. Raloxifene-Like SERMs

4.2.1.. Arzoxifene (LY353381)

4.2.2.. Lasofoxifene (CP-336156, Fablyn)

4.2.3.. Pipendoxifene (ERA-923)

4.2.4.. Bazedoxifene (TSE-424, WAY-140424)

4.2.5.. Acolbifene (EM-652, SCH57068) and EM-800 (SCH57050)

4.2.6.. CHF4227

4.2.7.. SP500263

4.3.. Steroidal SERMs

4.3.1.. HMR3339

4.3.2.. PSK3471

4.4.. ER Subtype Selective SERMs

4.4.1.. Discovery of New Properties of SERMs

5.. CONCLUDING REMARKS

DISCLOSURE

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

REFERENCES

Targeting Leukemia Stem Cells with Novel Therapeutic Agents

Abstract

Introduction

Leukemia Stem Cells

Novel therapeutic drugs against LSCS

Alox5 Inhibitor

Hsp90 Inhibitors

Omacetaxine

Hedgehog Inhibitor

BMS-214662

CONCLUSIONS

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

DISCLOSURE

REFERENCES

Targeting Migrating Cells in Glioblastoma

Abstract

Introduction

EGFR and Related Growth Factor Pathways

Transforming Growth Factor β (TGF-β) Receptors

Integrins

Immunoglobulin Family

G Protein-Coupled Receptors (GPCRS)

Signaling Molecules

GBM stem cells

Other Mechanisms responsible for migration

Unexplored factors in migration

Conclusions: Treatment Outlook and Promising Developments

Conflict of interest

ACKNOWLEDGEMENTs

Disclosure

REFERENCES

Tyrosyl-DNA Phosphodiesterase 1 as a Target for Anticancer Therapy

Abstract

1.. INTRODUCTION

2.. TOPOISOMERASE I

2.1.. Biological Functions and Catalytic Mechanism

2.2.. The Formation of Irreversible Top1 Cleavage Complexes

3.. TYROSYL-DNA PHOSPHODIESTERASE

3.1.. Discovery and Physiological Function of Tdp1

3.2.. Structure and Catalytic Mechanism of Tdp1

3.3.. Tdp1 Substrates

3.4.. Tdp1-Dependent Repair Pathway

3.5.. Tdp1-Independent Repair Pathways

3.6.. Rationale for Targeting Tdp1 for Cancer Therapy

3.7.. Tdp1 Inhibitors

4.. SUMMARY AND PERSPECTIVES

CONFLICT OF INTEREST

ACKNOWLEDGEMENTs

DISCLOSURE

REFERENCES

Advances in Anticancer Agents in

Medicinal Chemistry

Volume 2

Edited By:

Michelle Prudhomme

Institut de Chimie de Clermont-Ferrand ICCF

CNRS UMR 6296 24 Avenue des Landais 63177 Aubiere Cedex

France

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FOREWORD

This eBook in the Advances in Anticancer Agents in Medicinal Chemistry series continues the concept put together so well in the first volume of the series. By drawing on original articles published during 2008-2010 in Anticancer Agents in Medicinal Chemistry, and having them updated, the volume provides up-to-date reviews on a wide range of drug classes, including marine macrolides, metal-based complexes and glycoconjugate-based vaccines. Also discussed are biological targets through which to control leukemia stem cells, mitosis, metastasis, DNA repair and estrogen receptor modulation. Michelle Prudhomme, Editor-in-Chief of Anticancer Agents in Medicinal Chemistry, is to be commended for this new series, and for the selection of such a wide-ranging set of interesting reviews in Volume 2.

PREFACE

In Volume 2 of the eBook series Advances in Anticancer Agents in Medicinal Chemistry are gathered chapters on several classes of molecules exhibiting anticancer potentialities as well as some important targets for the development of novel anticancer drugs.

Marine macrolides are fascinating molecules with a large number of chiral centers. In the first chapter of Volume 2, Antonio H. Daranas, José J. Fernández and colleagues discuss the potential of marine macrolides in cancer therapy. Various families of marine macrolides and their biological targets are presented.

Since the discovery of cisplatin, a huge interest has been paid to metal-based complexes as anticancer drugs. The second chapter by Chang-He Zhou et al. reviews the recent research and development of organometallic supramolecular complexes as anticancer agents. Whereas in the third chapter, Dolores Fregona and colleagues develop the potential of gold-based anticancer agents, in particular gold(III)-dithiocarbamato complexes which, due to their lower toxicity compared to the platinum drugs, could provide an interesting alternative.

In the search for anticancer vaccines, recent synthetic strategies towards glycoconjugates have been developed. These strategies and the development of glyconanoparticles are reviewed by Laura Cipolla and co-workers.

Isatin is an oxidised derivative of indole. Various substituted isatins exhibiting anticancer properties have been identified in plants and microorganisms. Isatin is a simple and excellent scaffold for the construction of new compounds of biological interest. Kara L. Vine, Lidia Matesic and colleagues summarize the recent structure-activity relationship studies on isatin-based compounds as anticancer agents.

The tripentone family represents a promising class of compounds, some of them exhibiting a potent cytotoxicity towards cancer cells. In their chapter, Patrick Dallemagne and collaborators review the different synthetic routes to tripentones and the emergence of the highly cytotoxic MR22388.

Endocrine therapy targeting to estrogen receptors (ER) and especially ER alpha has been very successful in the treatment and prevention of breast cancer. Virgil C. Jordan and co-workers provide an excellent update on the potential of selective estrogen receptor modulators.

Leukemia stem cells (LSCs) are defined as a small cell population required for the initiation and maintenance of leukemia. The chapter by Shaoguang Li and collaborators gives an overview on the development of new therapeutic strategies and drugs targeting LSCs.

Glioblastoma (GBM) is an aggressive disease associated with a poor prognostic due to a rapid migration of the GBM cells. In this review, Cory Adamson and colleagues describe various potential targets that may be exploited to inhibit the migration GBM cells.

The last chapter by Yves Pommier et al. is devoted to a DNA repair protein Tyrosyl-DNA phosphodiesterase 1 (Tdp1), an enzyme implicated in the repair of irreversible Top1-DNA covalent complexes. Rationale for the development of Tdp1 inhibitors for cancer therapy is discussed.

Marine Macrolides: Blue Biotechnology Against Cancer

José G. Napolitano1,Antonio H. Daranas*,1,2,Manuel Norte1,José J. Fernández*,1

1Instituto Universitario de Bioorgánica “Antonio González”, Astrofísico Fco. Sánchez 2, Universidad de La Laguna, La Laguna 38206, Canary Islands, Spain; 2Departamento de Ingeniería Química y Tecnología Farmacéutica, Astrofísico Fco. Sánchez 2, Universidad de La Laguna, La Laguna 38071, Canary Islands, Spain

Abstract

Chemical study of marine organisms has revealed them as a rich source of natural products with unique structural characteristics and outstanding biological activities. Marine macrolides are a unique group of natural products that frequently include a highly oxygenated polyene backbone and a macrocyclic lactone as a conformational constraint. Many of them have shown unparalleled cell growth antiproliferative properties, making them valuable molecular probes for the discovery of new biochemical pathways or as promising lead compounds in the development route to new antitumor chemotherapeutic agents. This bibliographic review has been focussed on marine macrolides with strong cytotoxic activity and potential in cancer research and therapy, as well as those macrolides either in the market or currently in clinical trials and/or preclinical development.

Keywords:: Marine macrolides, antitumor agents, blue biotechnology, natural products, cytotoxicity, cancer.

*Address correspondence to Antonio H. Daranas and José J. Fernández: Instituto Universitario de Bioorgánica “Antonio González”, Astrofísico Fco. Sánchez 2, Universidad de La Laguna, La Laguna 38206, Canary Islands, Spain; Tel: [phone]; Fax: [phone]; E-mail: [email protected]; [email protected]

Conflict of interest

The authors declare that there is no conflict of interest.

ACKNOWLEDGEMENTS

This work was supported by Spanish Ministerio de Economía y Competitividad (SAF2011-28883-C03-01).

Disclosure

This e-Book chapter is an updated version of the article entitled “Marine Macrolides, a Promising Source of Antitumor Compounds” published in Anti-Cancer Agents in Medicinal Chemistry, 2009, 9(2), 122-137.

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