title: Photoactivated DNA cleavage and anticancer activity of pyrenyl-terpyridine lanthanide complexes.
abstract: Lanthanide(III) complexes [Ln(R-tpy)(acac)(NO(3))(2)] (Ln = La(III) in 1, 2; Gd(III) in 4, 5) and [Ln(py-tpy)(sacac)(NO(3))(2)] (Ln = La(III), 3; Gd(III), 6), where R-tpy is 4'-phenyl-2,2':6',2″-terpyridine (ph-tpy in 1, 4), 4'-(1-pyrenyl)-2,2':6',2″-terpyridine (py-tpy in 2, 3, 5 and 6), acac is acetylacetonate and sacac is 4-hydroxy-6-{4-[(β-d-glucopyranoside)oxy]phenyl}hex-3,5-dien-2-onate, were prepared to study their DNA photocleavage activity and photocytotoxicity. Complexes [La(ph-tpy)(acac)(EtOH)(NO(3))(2)] (1a) and [Gd(ph-tpy)(acac)(NO(3))(2)] (4) were characterized by X-ray crystallography. The 1:1 electrolytic complexes bind to calf thymus DNA. The py-tpy complexes cleave pUC19 DNA and exhibit remarkable photocytotoxicity in HeLa cells in UV-A light of 365 nm with apoptotic cell death (IC(50): ∼40 nM in light, >200 μM in dark). Confocal microscopy using HeLa cells reveal primarily cytosolic localization of the complexes.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560012, India.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Hussain
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Gadadhar
authors.forename: Tridib K
authors.initials: TK
authors.lastname: Goswami
authors.forename: Anjali A
authors.initials: AA
authors.lastname: Karande
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects* / Q000528:radiation effects*; D006367:HeLa Cells; D006801:Humans; D028581:Lanthanoid Series Elements / Q000737:chemistry* / Q000494:pharmacology*; D008956:Models, Chemical; D015394:Molecular Structure; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D028581:Lanthanoid Series Elements; D017319:Photosensitizing Agents; D004247:DNA; C427203:calf thymus DNA