Two mixed-NH3/amine platinum (II) anticancer complexes featuring a dichloroacetate moiety in the leaving group

Abstract

Two mixed-NH3/amine platinum (II) complexes of 3-dichoroacetoxylcyclobutane-1, 1-dicarboxylate have been prepared in the present study and characterized by elemental analysis and IR, HPLC-MS and 1H, 13C-NMR. The complexes exist in equilibrium between two position isomeric forms and undergo hydrolysis reaction in aqueous solution, releasing the platinum pharmacophores and dichloroacetate which is a small-molecular cell apoptosis inducer. Both complexes were evaluated for in vitro cytotoxic profile in A549, SGC-7901 and SK-OV-3 caner cells as well as in BEAS-2B normal cells. They exhibit markedly cytoxicity toward cancer cells by selectively inducing the apoptosis of cancer cells, whereas leaving normal cells less affected. They have also the ability to overcome the resistance of SK-OV-3 cancer cells to cisplatin. Our findings offer an alternative novel way to develop platinum drugs which can both overcome the drug resistance and selectively target tumor cells.

Cytotoxic performances of new anionic cyclometalated Pt(II) complexes bearing chelated O^O ligands

“…It has been reported that the Pt(II) anticancer drug cycloplatam, important for overcoming drug resistance to cisplatin (Chart 4), occurs in two isomeric cis / trans forms, the biological activity of any single isomeric form remaining at first unknown. Recently, the two bioactive isomers have been separated and tested showing equal anticancer activity …”

Ruthenium Polypyridyl Complex Inhibits Growth and Metastasis of Breast Cancer Cells by Suppressing FAK signaling with Enhancement of TRAIL-induced Apoptosis

“…Ruthenium (Ru) complexes have attracted much attention as building blocks for novel metal-based anticancer and antimetastatic drugs since the discovery of cisplatin and the successful application of other platinum (Pt) complexes 8 9 10 . During the past three decades, a large number of potential Ru complexes have exhibited utility in chemotherapy, and some of them, including NAMI-A and KP1019, have entered into human clinical trials 8 11 .…”

Design, synthesis and anticancer activity of diam(m)ine platinum(II) complexes bearing a small-molecular cell apoptosis inducer dichloroacetate

“…Introduction of a dichloroacetate moiety into cyclobutane-1,1-dicarboxylic acid had been previously described in our report [18]. Shortly, K 2 PtCl 4 was first converted to K 2 PtI 4 in situ by the treatment with KI, followed by addition of 2NH 3 or diamines, forming an insoluble diam(m)inediiodoplatinum(II) intermediate.…”

“…3-Dichoroacetoxylcyclobutane-1,1-dicarboxylic acid and (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane were prepared as previously described [18,19]. All other chemicals obtained from commercial suppliers were of analytical grade and used as received.…”

“…Based on the above findings, we previously synthesized two mixed-NH 3 /amine (amine = cyclopentylamine, cyclohexylamine) platinum(II) complexes featuring a dichloroacetate moiety tethered to the leaving group via an ester bond [18]. They exhibited markedly cytotoxicity toward cancer cells by selectively inducing the apoptosis of cancer cells, resulting in the decreased resistance of SK-OV-3 cancer cells to cisplatin.…”