Abstract
DNA topoisomerases are an important family of enzymes that catalyze the induction of topological changes in the DNA molecule. Their ability to modulate the topology of the DNA makes DNA topoisomerases a key player in several vital cell processes such as replication, transcription, chromosome separation and segregation. Consequently, they already represent an important collection of macromolecular targets for some of the established anticancer drugs on the market as well as serve as templates in the development of novel anticancer drugs especially supported by recent structural advances in the field.
The aim of this review is to provide an overview of the recent developments in the field of DNA poisons - a major class of human topoisomerase IIα inhibitors - of which several are already in clinical use. Due to frequently experienced occurrence of serious side effects of these molecules during therapy, especially cardiotoxicity issues, further drug design efforts were initiated already yielding novel promising compounds that have overcome this issue and already entered into clinical studies. Some of the presented and discussed chemical classes include intercalators, non-intercalators and redox-dependent poisons of human topoisomerase IIα. In particular, this review focuses on the currently available structure-based standpoint of molecular design and on the medicinal chemist’s perspective of this field of anticancer drug design.
Keywords: DNA topoisomerase IIα, DNA poisons, intercalators, non-intercalators, redox-dependent poisons, inhibitors, anticancer agents, medicinal chemistry, drug design, cardiotoxicity
Current Pharmaceutical Design
Title:Recent Developments of DNA Poisons - Human DNA Topoisomerase IIα Inhibitors - as Anticancer Agents
Volume: 19 Issue: 13
Author(s): Barbara Pogorelcnik, Andrej Perdih and Tom Solmajer
Affiliation:
Keywords: DNA topoisomerase IIα, DNA poisons, intercalators, non-intercalators, redox-dependent poisons, inhibitors, anticancer agents, medicinal chemistry, drug design, cardiotoxicity
Abstract: DNA topoisomerases are an important family of enzymes that catalyze the induction of topological changes in the DNA molecule. Their ability to modulate the topology of the DNA makes DNA topoisomerases a key player in several vital cell processes such as replication, transcription, chromosome separation and segregation. Consequently, they already represent an important collection of macromolecular targets for some of the established anticancer drugs on the market as well as serve as templates in the development of novel anticancer drugs especially supported by recent structural advances in the field.
The aim of this review is to provide an overview of the recent developments in the field of DNA poisons - a major class of human topoisomerase IIα inhibitors - of which several are already in clinical use. Due to frequently experienced occurrence of serious side effects of these molecules during therapy, especially cardiotoxicity issues, further drug design efforts were initiated already yielding novel promising compounds that have overcome this issue and already entered into clinical studies. Some of the presented and discussed chemical classes include intercalators, non-intercalators and redox-dependent poisons of human topoisomerase IIα. In particular, this review focuses on the currently available structure-based standpoint of molecular design and on the medicinal chemist’s perspective of this field of anticancer drug design.
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Pogorelcnik Barbara, Perdih Andrej and Solmajer Tom, Recent Developments of DNA Poisons - Human DNA Topoisomerase IIα Inhibitors - as Anticancer Agents, Current Pharmaceutical Design 2013; 19 (13) . https://dx.doi.org/10.2174/1381612811319130016
DOI https://dx.doi.org/10.2174/1381612811319130016 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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