Synthesis of Ag(I) camphor sulphonylimine complexes and assessment of their cytotoxic properties against cisplatin-resistant A2780cisR and A2780 cell lines.
Camphorsulphonylimine complexes [Ag(NO3)(IL)2] (IL=C12H19N3SO2, 1) and [(AgNO3)2(IIL)] (IIL=C22H23N3SO2, 2) were synthesized and characterized by elemental analysis, spectroscopy (IR, NMR) and cyclic voltammetry. [Ag(NO3)(IL)2] crystalizes in the monoclinic C2 space group with a triangular geometry assuming a chalice-type shape. The anti-proliferative properties of the new complexes 1 and 2 and those of the previously reported [Ag(NO3)(IIIL)] (IIIL=C16H18N3SO2, 3) were assessed against the human ovarian cancer cells (cisplatin-sensitive A2780, cisplatin-resistant A2780cisR) and the non-tumoral human HEK 293 cell line, using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The NR (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) assay was alternatively used to assess the cytotoxicity on the A2780 cells. Results from the MTT assay (48h exposure) show that the complexes display IC50values lower (by at least one order of magnitude) than cisplatin, while the cytotoxicity of AgNO3is of the same order of cisplatin. The camphorsulphonylimine ligands display irrelevant (IL,IIIL) or no cytotoxicity (IIL). The highest cytotoxicity (lower IC50) was found for [(AgNO3)2(IIL)]. The binding ability of the complexes to calf thymus-deoxyribonucleic acid (CT-DNA) was studied by fluorescence. Constants (Ksv, Ka) and the number (n) of binding centres to DNA were calculated showing that DNA intercalation possibly occurs in the cases of complexes 2 and 3, while a more complicated process operates for 1. As expected from the cytotoxicity, [(AgNO3)2(IIL)] displays the highest binding affinity (Ka=1.61×105 M-1). No binding to DNA was detected for AgNO3orIIL under the experimental conditions used. The binding trend to CT-DNA found by fluorescence was corroborated by cyclic voltammetry.
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1049-001, Lisboa, Portugal.
João M S
JMS
Cardoso
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1049-001, Lisboa, Portugal.
Isabel
I
Correia
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1049-001, Lisboa, Portugal.
Adelino M
AM
Galvão
Centro de Ciências e Tecnologias Nucleares (C(2)TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
Fernanda
F
Marques
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1049-001, Lisboa, Portugal. Electronic address: fcarvalho@ist.utl.pt.
M Fernanda N N
MFNN
Carvalho
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002164:Camphor / Q000737:chemistry / Q000493:pharmacokinetics; D002945:Cisplatin / Q000494:pharmacology*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012834:Silver / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007097:Imines; D012834:Silver; D002164:Camphor; D002945:Cisplatin
Camphorsulphonylimines; Cytotoxic properties; DNA binding; Silver complexes; Synthesis