title: In vitro anticancer activity of gold(III) complexes with some esters of (S,S)-ethylenediamine-N,N'-di-2-propanoic acid.
abstract: Five novel gold(III) complexes of general formulas [AuCl2{(S,S)-R2eddip}]PF6, ((S,S)-eddip = (S,S)-ethylenediamine-N,N'-di-2-propanoate, R = n-Bu, n-Pe, i-Bu, i-Am, cPe; 1-5, respectively) were synthesized and characterized by UV/Vis, IR and NMR spectroscopy and mass spectrometry. DFT calculations indicated that (R,R)-N,N'-configuration diastereoisomers were the most stable for 1-5. 3 is stable in DMSO for at least 24 h, but immediate hydrolysis in PBS occurs. 3 is readily reduced with ascorbic acid and forms adducts with bovine serum albumin (BSA). In vitro anticancer activity of the gold(III) complexes against human cervix adenocarcinoma HeLa, human myelogenous leukemia K562, human melanoma Fem-x tumor cell lines, as well as against non-cancerous human embryonic lung fibroblast cell line MRC-5 was determined using MTT assay. Complex 4 showed highest activity and selectivity (IC50(Fem-x) = 1.3 ± 0.2; IC50(MRC-5)/IC50(Fem-x) = 72.5 ± 12.4), 4 times more active and 28 times more selective than cisplatin. Complexes induced apoptotic mode of death in a time-dependent manner in HeLa cells.
authors.affiliation: Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11080 Belgrade-Zemun, Serbia.
authors.forename: Nebojša
authors.initials: N
authors.lastname: Pantelić
authors.affiliation: Institute of Oncology and Radiology, 11000 Belgrade, Serbia.
authors.forename: Tatjana P
authors.initials: TP
authors.lastname: Stanojković
authors.affiliation: Department of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studenski Trg 14, 11000 Belgrade, Serbia.
authors.forename: Bojana B
authors.initials: BB
authors.lastname: Zmejkovski
authors.affiliation: Faculty of Chemistry, University of Belgrade, P. O. Box 158, 11001 Belgrade, Serbia. Electronic address: tsabo@chem.bg.ac.rs.
authors.forename: Tibor J
authors.initials: TJ
authors.lastname: Sabo
authors.affiliation: Department of Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle (Saale), Germany. Electronic address: goran.kaluderovic@ipb-halle.de.
authors.forename: Goran N
authors.initials: GN
authors.lastname: Kaluđerović
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005029:Ethylenediamines / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011422:Propionates / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D005029:Ethylenediamines; D050607:Organogold Compounds; D011422:Propionates; C000601853:ethylenediamine-N,N'-di-2-propanoic acid
keywords: Apoptosis; Cell cycle; Cytotoxicity; DFT; Gold(III) complexes; R(2)edda-type ligands