A new class of platinum(ii) complexes with the phosphine ligand pta which show potent anticancer activity

Abstract

The anticancer potential of sixteen platinum(II) complexes with general formulae [PtCl(hq)(S-dmso)] (1a-8a) and [PtCl(hq)(pta)] (1b-8b) (where hq is 5-chloro-7-iodo-8-quinolinol (clioquinol; cqH) (1a, 1b), 8-hydroxy-5-nitroquinoline (nitroxoline; nxH) (2a, 2b), 5,7-dichloro-8-quinolinol (3a, 3b), 5,7-diiodo-8-quinolinol (4a, 4b), 5,7-dibromo-8-quinolinol (5a, 5b), 5,7-dichloro-8-hydroxy-2-methyl-quinoline (6a, 6b), 8-hydroxyquinoline (7a, 7b) and 8-quinolinethiol (8a, 8b); dmso is dimethyl sulfoxide and pta is 1,3,5-triaza-7-phosphaadamantane) was determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and A549) and embryotoxicity assay in a zebrafish model. Interactions with double stranded DNA through in vitro assay and a molecular docking study were examined. All complexes, except 6a, exhibited a high cytotoxic effect on MRC5 cells at a concentration of 10 µg mL −1 while 1b, 5a, 6a and 3b showed selective toxicity towards carcinoma cell lines. In general, were 1b, 3b, 6b and 5b. From observations of the DNA interaction ability and of the in silico assessment, no apparent DNA fragmentation was observed either on DNA extracted from the treated cancer cell line or from the zebrafish embryos.

New Findings in Metal Complexes with Antiproliferative Activity Containing 1,3,5‐Triaza‐7‐phosphaadamantane (PTA) and Derivative Ligands

“…[27] Other attractive complexes are the neutral [Ru(N-N)-(PTA) 2 Cl 2 ] {N-N = bpy (10), N-N = phen (11)}, monocationic [Ru(N-N)(PTA) 3 Cl]Cl {N-N = bpy (12), N-N = phen(13)} and, di-Scheme 1. [29][30][31] It was showed that the co-ligands bonded to the {Pt(2,2-bpy)} + moiety have a large influence on the reaction kinetics of the complexes with biomolecules such as amino acids, proteins, and DNA. Adapted from ref.…”

“…Complex 11 was found to be the most effective in blocking cell cycle, inducing also necrotic cell death in Multiple Myeloma (MM) cell lines. [31] Scheme 3. Scheme 2.…”

“…[28] Homeostasis of organisms depends on an intricate balance between cell death and renewal, which could be disrupted by diseases and external agents. [31] Even if Ru and Pt complexes are the most popular among the antiproliferative metal compounds, the Re-PTA, Re-DAPTA and Re-THP complexes [Re(CO) 3 Synthesis and structure of complexes 10-15.…”

Probing of effective pyrazolone based metallonucleases: Molecular docking and in vitro biological critiques

“…Conformation of docked small molecules was analyzed in terms of energy, hydrogen bonding and hydrophobic interaction between the complexes and receptor. The predicted top‐ranking pose with the complexes lowest energy was used to suggest the best possible geometry of the complex inside the receptor (targets) and highest binding affinity between the desired compound (ligand and complexes) and macromolecule . In this study, the binding affinity of the synthesized compounds was performed by Hex 8.0 software against the macromolecules (receptor) of nucleic acid (1BNA) and protein (3hb5), which is an interactive molecular graphics program to understand the drug‐DNA interactions .…”

Biological evaluation of rare earth complexes bearing 1H‐imidazo[4,5‐f]‐1,10‐phenanthroline moiety as promising anticancer chemotherapeutics

“…Efforts focused on minimizing the toxic effects of metallodrugs in clinical treatment have been substantial in the preclinical field, with metal‐based cancer drugs developing while continuing to mature . From cisplatin to the second‐generation carboplatin and the third‐generation oxaliplatin, all of them have made a significant contribution to the successful treatment of cancer patients .…”