title: Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents.
abstract: Acridine derivatives have been explored as DNA-binding anticancer agents. Some derivatives show undesired pharmacokinetic properties and new derivatives need to be explored. In this work, a series of novel acridine analogues were synthesized by modifying previously unexplored linkers between the acridine and benzene groups and their antiproliferative activity and the DNA-binding ability were evaluated. Among these derivatives, compound 5c demonstrated DNA-binding capability and topoisomerase I inhibitory activity. In K562 cell lines, 5c induced apoptosis through mitochondria-dependent intrinsic pathways. These data suggested that compound 5c and other acridine derivatives with modified linkers between the acridine and benzene groups might be potent DNA-binding agents.
authors.affiliation: Tsinghua University, Department of Chemistry, Beijing 100084, PR China.
authors.forename: Xuliang
authors.initials: X
authors.lastname: Lang
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.forename: Yuzong
authors.initials: Y
authors.lastname: Chen
authors.forename: Qinsheng
authors.initials: Q
authors.lastname: Sun
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tan
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Gao
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000166:Acridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D004247:DNA