人DNA拓扑异构酶Ⅱα抑制剂的生物测定及硅胶鉴定

Title:Bioassays and In Silico Methods in the Identification of Human DNA Topoisomerase IIα Inhibitors

Volume: 25 Issue: 28

关键词: 人dna拓扑异构酶IIα，催化抑制剂，脱氧核糖核酸毒物，抗癌药物，生物分析，药物化学。

摘要: Background: The family of DNA topoisomerases comprises a group of enzymes that catalyse the induction of topological changes to DNA. These enzymes play a role in the cell replication machinery and are, therefore, important targets for anticancer drugs - with human DNA topoisomerase IIα being one of the most prominent. Active compounds targeting this enzyme are classified into two groups with diverse mechanisms of action: DNA poisons act by stabilizing a covalent cleavage complex between DNA and the topoisomerase enzyme, transforming it into a cellular toxin, while the second diverse group of catalytic inhibitors, provides novel inhibition avenues for tackling this enzyme due to frequent occurrence of side effects observed during the DNA poison therapy.

Methods: Based on a comprehensive literature search we present an overview of available bioassays and in silico methods in the identification of human DNA topoisomerase IIα inhibitors.

Results and Conclusion: A comprehensive outline of the available methods and approaches that explore in detail the in vitro mechanistic and functional aspects of the topoisomerase IIα inhibition of both topo IIα inhibitor groups is presented. The utilized in vitro cell-based assays and in vivo studies to further explore the validated topo IIα inhibitors in subsequent preclinical stages of the drug discovery are discussed. The potential of in silico methods in topoisomerase IIα inhibitor discovery is outlined. A list of practical guidelines was compiled to aid new as well experienced researchers in how to optimally approach the design of targeted inhibitors and validation in the preclinical drug development stages.

Cite this article as:

Bioassays and In Silico Methods in the Identification of Human DNA Topoisomerase IIα Inhibitors, Current Medicinal Chemistry 2018; 25 (28) . https://dx.doi.org/10.2174/0929867325666180306165725