title: Luminescent cyclometalated platinum(II) complex forms emissive intercalating adducts with double-stranded DNA and RNA: differential emissions and anticancer activities.
abstract: Luminescent metallo-intercalators are potent biosensors of nucleic acid structure and anticancer agents targeting DNAs. There are few examples of luminescent metallo-intercalators which can simultaneously act as emission probes of nucleic acid structure and display promising anticancer activities. Herein, we describe a luminescent platinum(II) complex, [Pt(C^N^N)(C≡NtBu)]ClO4 (1 a, HC^N^N= 6-phenyl-2,2'-bipyridyl), that intercalates between the nucleobases of nucleic acids, accompanied by an increase in emission intensity and/or a significant change in the maximum emission wavelength. The changes in emission properties measured with double-stranded RNA (dsRNA) are different from those with dsDNA used in the binding reactions. Complex 1 a exhibited potent anticancer activity towards cancer cells in vitro and inhibited tumor growth in a mouse model. The stabilization of the topoisomerase I-DNA complex with resulting DNA damage by 1 a is suggested to contribute to its anticancer activity.
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong (China).
authors.forename: Taotao
authors.initials: T
authors.lastname: Zou
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Ching Tung
authors.initials: CT
authors.lastname: Lum
authors.forename: Chensheng
authors.initials: C
authors.lastname: Ma
authors.forename: Ruth Chau-Ting
authors.initials: RC
authors.lastname: Chan
authors.forename: Chun-Nam
authors.initials: CN
authors.lastname: Lok
authors.forename: Wai-Ming
authors.initials: WM
authors.lastname: Kwok
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D049449:Luminescence; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D012330:RNA, Double-Stranded; D004247:DNA
keywords: DNA; anticancer; exciplex emission; platinum; topoisomerase I