Topoisomerase Inhibitors: Classification, Mechanisms of Action & Adverse Effects

This book aims to assist the scientists working with the medicinal, biochemical, biophysical, genetic and pharmacological aspects of topoisomerases and their inhibitors. The book has covered various aspects of topoisomerases like classification, structural aspects, basic genetics and mutations, disease implications and cell signaling networks, which may be helpful for researchers of the field for better therapeutics. Chapter One deals with structure, functions and role and of human topoisomerase-I in cancer progression. It describes a detailed classification, mechanism of action and recent updates on the development of camptothecin and non-camptothecin derivatives, along with their Structure-Activity Relationships (SAR) as topoisomerase-I inhibitors. Chapters Two and Three cover X-ray co-crystal structures, biological functions and the significant role of topoisomerase-II isoforms in cancer. A thorough discussion on classification and various pharmacoinformatics techniques employed in delineating the binding mode of topoisomerase-II inhibitors and their mechanism of action is well presented. Chapter Four deals not only with adverse effects associated with the use of topoisomerase-I and II inhibitors, but also includes approaches to overcome them. Chapter Five discusses various disorders associated with SNPs in topoisomerases and risks associated with their pharmacogenetics. Chapter Six sheds light on interactions and cross-talks between topoisomerases and histone deacetylases, leading to their significant role in drug resistance. The work is expected to assist the scientists to selectively design dual/multi-inhibitors of topoisomerases and histone deacetylases. The authors are thankful to the reviewers, who were so kind in reviewing and making suggestions for improving this book. This book could not have been completed without their commendable efforts.