Tin-Based Antitumour Drugs

ISBN-13: 9783642741937 / Angielski / Miękka / 2011 / 226 str.

Marcel Gielen

Opis

Whereas platinum compounds are already clinically used as anticancer agents, tin compounds exhibiting high enough antitumour activity have not yet been found to enter the clinical phase. This is paradoxical with the observation that 50% of the tested compounds showed some activity, which is an abnormally high percentage. This is probably due to the fact that research of this type with tin compounds started more recently than with platinum compounds and that almost exclusively known compounds coming from laboratories working in the field of organotin compounds have been blindly tested. Some research directed towards the development of organotin compounds with some biologically favourable properties, for instance derivatives with hydrophilic or lipophilic, or with increased bio-availability characteristics, has started only recently. We thought that was now the appropriate time to bring together experts from different disciplines (biochemists, pharmacologists, organotin chemists, oncologists, etc.) working in the field of tin-based antitumour drugs, to contribute to the critical assessment of existing knowledge in this new important topic, to identify the directions for future research and to promote close working relations between the different countries and professional experiences gathered in this workshop.

Spis treści

The Role of Non-Platinum Complexes in Cancer Therapy.- Tumor-Inhibiting Metal Complexes and the Development of Cisplatin.- The Development of New Tumor-Inhibiting Metal Complexes.- Fundamental Strategies.- Methods.- Synthesis of Direct Derivatives of Cisplatin.- Basic Ideas.- The Development of Non-Platinum Complexes.- Non-Platinum Complexes in Preclinical Trials.- Tumor-inhibiting Ruthenium Complexes.- Non-Platinum Complexes in Clinical Studies.- Gallium and Germanium Compounds in Clinical Studies.- Preclinical and Clinical Development of Budotitane.- Structure-Activity Relation of Tumor-Inhibiting Bis(?-diketonato) Metal Complexes.- Variation of the (?-Diketonato) Ligand.- Variation of the Central Metal.- Variation of the Group X.- Antitumor Activity in Other Transplantable Tumor Models.- Therapy Results on Autochtonous, AMMN-Induced, Colorectal Tumors with Budotitane.- Toxicity of Budotitane.- Budotitane Clinical Phase I Study.- Drug Targeting.- Perspectives.- References.- Tin Compounds and their Potential as Pharmaceutical Agents.- Tin Protoporphyrin for the Treatment of Neonatal Jaundice.- Antitumour Properties of Tin Chemicals.- Mode of Action.- The Use of Tin Derivatives in the Photodynamic Therapy of Cancer.- Tin Derivatives as Antiviral Agents.- Other Pharmaceutical Uses.- Conclusion.- Acknowledgements.- References.- The Role of Natural Tin Hormones in Senescence: a Hypothesis.- Background: Immune Involvement.- Background: Geroprotective Effects of Tin.- Capitulation.- Ontogeny of the Immune System.- Immune Theory of Aging.- Thymus-Pineal Axis.- Life Pattern Hypothesis.- Tin Deprivation and Life Span.- Tin and the Life Pattern.- Summary.- References.- The Speciation and Bioavailability of Tin in Biofluids.- Historical Outline.- Speciation Studies.- Experimental.- Materials.- Procedure.- Results.- Formation Constants Measurement.- Regression Analysis.- Speciation Modelling.- Discussion.- Tin in Canned Food.- Bioavailability.- Toxicity and Essentiality.- Conclusions.- Acknowledgements.- References.- Cellular Interactions of Organotin Compounds in Relation to their Antitumor Activity.- Direct Cytotoxic Effects.- Disturbances of Mitochondrial Energetics in vitro.- Disturbances of Cellular Energetics in vitro.- Disturbances of Macromolecular Synthesis in vitro.- Summary and Conclusions on the Cellular Effects of Organotins.- Vivo-Vitro Relation of Antitumour Activity of Organotins.- Mode of Action of Organotins in Relation to their Antitumor Activity.- References.- Selectivity of Antiproliferative Effects of Dialkyltin Compounds in vitro and in vivo.- Computer Assisted Structure-Activity Correlations of Organotin Compounds as Potential Anticancer and Anti-HIV Agents.- Results.- Discussion.- Conclusions.- References.- Route of Administration is a Determinant of the Tissue Disposition and Effects of TBTO on Cytochrome P-450-Dependent Drug Metabolism.- Materials and Methods.- Results and Discussion.- Acknowledgements.- References.