title: Homoleptic phosphino copper(I) complexes with in vitro and in vivo dual cytotoxic and anti-angiogenic activity.
abstract: Homoleptic, tetrahedral Cu(i) complexes of the type [Cu(P)4]BF4 (1-3), where P are the phosphine ligands, 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) and 2-thia-1,3,5-triaza-phosphoaadamantane-2,2-dioxide (PTA-SO2), have been prepared. Novel complexes [Cu(DAPTA)4]BF42 and [Cu(PTA-SO2)4]BF43 have been fully characterized by means of spectroscopic methods, corroborated by XAS-EXAFS analysis of 2. In vitro cell culture experiments revealed a significant antiproliferative activity for Cu(i) compounds against several human cancer cell lines derived from solid tumors with preferential cell growth inhibition towards tumour compared to non-malignant cells. In vitro monitoring of migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs) showed an anti-angiogenic effect of copper(i) complexes at sub-cytotoxic concentrations. In vivo studies on the antitumor efficacy and ability to inhibit angiogenesis confirmed the dual cytotoxic and anti-angiogenic properties of Cu(i) derivatives.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Padova, via Marzolo 5, 35131 Padova, Italy. cristina.marzano@unipd.it.
authors.forename: V
authors.initials: V
authors.lastname: Gandin
authors.forename: A
authors.initials: A
authors.lastname: Trenti
authors.forename: M
authors.initials: M
authors.lastname: Porchia
authors.forename: F
authors.initials: F
authors.lastname: Tisato
authors.forename: M
authors.initials: M
authors.lastname: Giorgetti
authors.forename: I
authors.initials: I
authors.lastname: Zanusso
authors.forename: L
authors.initials: L
authors.lastname: Trevisi
authors.forename: C
authors.initials: C
authors.lastname: Marzano
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D003300:Copper / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D009943:Organophosphorus Compounds; D010720:Phosphines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: C501763:1,3,5-triaza-7-phosphaadamantane; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009943:Organophosphorus Compounds; D010720:Phosphines; D003300:Copper; D000218:Adamantane