title: Drugs acting on the beta isoform of human topoisomerase II (p180).
abstract: Topoisomerase II is the target of several anticancer agents. The discovery of a second enzyme, called topoisomerase II beta, genetically distinct from alpha, prompted the investigation on the different functional roles of the two isoforms. Whereas the first recognized isozyme is essential for life due to its role in chromosome condensation and segregation, beta functions remained elusive, although its importance in neural development is appearing clearer. Topoisomerase II beta is regulated differently than alpha, and its level of expression does not change significantly during cell cycle. The presence of this isoform in non-proliferating cells suggests that drug preferentially aimed at beta may be active in slow growing tumors. Topoisomerase II poisons were hence evaluated in light of their selectivity toward one or the other isozyme, indicating how the beta isoform may represent an important target for selected classes of drugs. Newer compounds were also synthesized and tested for their potential antitumor activity and their topoisomerase II beta poisoning. The literature dealing with "old" and "new" drugs targeted at topoisomerase II is reviewed trying to link, whenever possible, selective poisoning and cytotoxic effects to chemical structures, in the hope to indicate new lead compounds that will contribute to unveil molecular determinants of selectivity.
authors.affiliation: Dept. of Pharmaceutical Sciences, University of Padova, via Marzolo 5, 35131 Padova, Italy. barbara.gatto@unipd.it
authors.forename: B
authors.initials: B
authors.lastname: Gatto
authors.forename: E
authors.initials: E
authors.lastname: Leo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II