title: DNA binding and antiproliferative activity toward human carcinoma cells of copper(II) and zinc(II) complexes of a 2,5-diphenyl[1,3,4]oxadiazole derivative.
abstract: The interaction of calf thymus DNA with [CuL(ClO(4))]ClO(4)·H(2)O (1) and [ZnLBr]Br·H(2)O (2) (L = 9,12,15,18,27,28-hexaaza-29-oxatetracyclo[24.2.1.0(2,7).0(20,25)]enneicosa-2,4,6,20,22,24,26,28(1)-octaene) dicationic complexes in aqueous solution at neutral pH, was investigated by variable-temperature UV-vis absorption, circular dichroism and fluorescence spectroscopy. The values of the DNA-binding constants of these complexes, determined by competitive binding spectrofluorimetric titrations of ethidium bromide (EB)-DNA solutions, are (6.7 ± 0.5) × 10(6) M(-1) for CuL(2+) and (4.7 ± 0.5) × 10(5) M(-1) for ZnL(2+). These data together with a through analysis of the spectroscopic behaviour consistently suggest that both compounds are effective DNA binders. Interestingly, the DNA-binding strength of these complexes has been found to be correlated to their in vitro cytotoxic activity toward human breast carcinoma cells, although the complex with lower DNA-binding affinity is more active. In fact, biological studies showed that when the compounds are delivered through the cell membrane by a lipidic carrier, the cell survival is sensibly reduced, up to 58% with 1 and to 31% with 2.
authors.affiliation: Dipartimento di Chimica S. Cannizzaro, Università degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Edificio 17, 90128 Palermo, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Terenzi
authors.forename: Mirco
authors.initials: M
authors.lastname: Fanelli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ambrosi
authors.forename: Stefano
authors.initials: S
authors.lastname: Amatori
authors.forename: Vieri
authors.initials: V
authors.lastname: Fusi
authors.forename: Luca
authors.initials: L
authors.lastname: Giorgi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Turco Liveri
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Barone
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008958:Models, Molecular; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010080:Oxazoles; D003300:Copper; D004247:DNA; C009012:2,5-diphenyloxazole; D015032:Zinc