title: Promising antiproliferative platinum(II) complexes based on imidazole moiety: synthesis, evaluation in HCT-116 cancer cell line and interaction with Ctr-1 Met-rich domain.
abstract: A series of imidazole based platinum(II) complexes were synthesised and evaluated for their cytotoxicity in HCT-116 cancer cell line, known for being partially resistant to cisplatin but sensitive to oxaliplatin. Lipophilicity was modulated by introducing differently long saturated and unsaturated chains at the N1 of the imidazole moiety. Pt-I displayed the higher cytotoxic effect achieving a IC50=38.0±14.1μM, comparable to the oxaliplatin value. The interaction between the imidazole platinum(II) complexes and the octapeptide called Mets7, the methionine-rich motif mimicking the N-terminal domain of the yCtr-1, was evaluated in order to have a major insight of the uptake and the eventual resistance mechanisms for the so-synthesised novel platinum compounds.
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy; Multimedica IRCCS, Via Milanese 300, 20099 Sesto San Giovanni, Italy.
authors: Nicola
authors: N
authors: Ferri
authors: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy.
authors: Giorgio
authors: G
authors: Facchetti
authors: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy.
authors: Sara
authors: S
authors: Pellegrino
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors: Chiara
authors: C
authors: Ricci
authors: Division of Experimental Therapeutics, Department of Medicine, Istituto Europeo di Oncologia, Via Giuseppe Ripamonti 435, 20141 Milano, Italy.
authors: Giuseppe
authors: G
authors: Curigliano
authors: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy.
authors: Elena
authors: E
authors: Pini
authors: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy. Electronic address: isabella.rimoldi@unimi.it.
authors: Isabella
authors: I
authors: Rimoldi
mesh_terms: D020816:Amino Acid Motifs; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D000079923:Copper Transporter 1; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D000077150:Oxaliplatin; D017434:Protein Structure, Tertiary
chemical_list: D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D056831:Coordination Complexes; D000079923:Copper Transporter 1; D007093:Imidazoles; D009842:Oligopeptides; D009944:Organoplatinum Compounds; C490079:SLC31A1 protein, human; D000077150:Oxaliplatin; C029899:imidazole; D002945:Cisplatin
keywords: Antiproliferative compound; HCT-116; Imidzazole; Mets7; Platinum(II) complex