title: Study of the synthesis, antiproliferative properties, and interaction with DNA and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic polyaromatic amines.
abstract: The chemical and biological features of two newly synthesized [PtCl2(L)(2-aminonaphthalene)] complexes (L is NH3 or 2-aminonaphthalene) were compared with those of two already reported enantiomeric complexes of formula [PtCl2(DABN)] [DABN is (R)-1,1'-binaphthyl-2,2'-diamine or (S)-1,1'-binaphthyl-2,2'-diamine]. Solution behavior, lipophilicity, cytotoxicity with regard to one colorectal (HCT116) and two ovarian (A2780 and A2780Cp8) human carcinoma cell lines, and in vitro DNA- and G-quadruplex-binding properties were evaluated. In particular, the cytotoxicity of [PtCl2(NH3)(2-aminonaphthalene)] was better than that of cisplatin for all cell lines, and rather resembled that of oxaliplatin. The solution behavior of the whole series of complexes and the absence of an evident relationship between lipophilicity and cytotoxicity seem to suggest that all these experimental parameters are probably smoothed out during the 3-day cytotoxicity experiments and do not strongly affect the half-maximal inhibitory concentrations. The results of electrophoretic studies indicate that different kinds of interaction with DNA can be involved in the mode of action of these complexes, with intercalation in double-stranded DNA and stacking on G-quadruplex DNA being strongly implicated in particular for [PtCl2(NH3)(2-aminonaphthalene)].
authors.affiliation: Dipartimento di Scienze e Innovazione Tecnologica (DiSIT), Università del Piemonte Orientale "Amedeo Avogadro", Viale Michel 11, 15121, Alessandria, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gabano
authors.forename: Sofia
authors.initials: S
authors.lastname: Gama
authors.forename: Filipa
authors.initials: F
authors.lastname: Mendes
authors.forename: Marzia B
authors.initials: MB
authors.lastname: Gariboldi
authors.forename: Elena
authors.initials: E
authors.lastname: Monti
authors.forename: Sophie
authors.initials: S
authors.lastname: Bombard
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bianco
authors.forename: Mauro
authors.initials: M
authors.lastname: Ravera
mesh_terms: D000588:Amines / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D002945:Cisplatin / Q000031:analogs & derivatives*; D004278:DNA, Superhelical / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011119:Polynucleotides / Q000378:metabolism*; D012996:Solutions
chemical_list: D000588:Amines; D002273:Carcinogens; D004278:DNA, Superhelical; D009944:Organoplatinum Compounds; D011119:Polynucleotides; D012996:Solutions; D002945:Cisplatin