Bifunctional Platinum(II) Complexes with Bisphosphonates Substituted Diamine Derivatives: Synthesis and In vitro Cytotoxicity

Abstract

A series of N,N'-dibisphosphonate-containing 1,3-propanediamine derivatives (L1 - L6) and their corresponding dichloridoplatinum(II) complexes (1 - 6) have been synthesized and characterized by elemental analysis, H-NMR, C-NMR, P-NMR and HR-MS spectra. The in vitro antitumor activities of compounds L1 - L6 and 1 - 6 were tested by WST-8 assay with Cell Counting Kit-8, indicating that platinum-based complexes 1 - 6 showed higher cytotoxicity than corresponding ligands L1 - L6 against A549 and MG-63, especially complex 2 which displayed comparable cytotoxicity to those of cisplatin and zoledronate after 48 h incubation. In addition, complexes 1 - 6 were more active in vitro on osteosarcoma cell line MG-63 than normal osteoblast cell line hFOB 1.19. The structure-activity relationship has been summarized based on the in vitro cytotoxicity of three series of platinum complexes from this and our previous studies. The in vitro bone affinity of platinum complexes was also tested by hydroxyapatite (HAP) chromatography in terms of capacity factor K'. Besides, in this paper, representative complex 2, which has been proved to be a promising antitumor agent with high cytotoxicity and bone HAP binding property, was investigated for its mechanism of action producing cell death against MG-63.

Multifunctional platinum(iv) complex bearing HDAC inhibitor and biotin moiety exhibits prominent cytotoxicity and tumor-targeting ability

“…[7][8][9][10][11] However, off-target interactions between the platinum(II) drugs and biomolecules not only decrease the therapeutic efficacy of the platinum(II) drugs but also result in more severe side effects compared with noncovalent organic drugs, which undoubtedly limit their application in clinical practice. [12][13][14][15][16] In addition, the inevitable drug resistance of platinum(II) drugs further limit their clinical utility. 17,18 Consequently, it is of great significance and a challenge to maximize the therapeutic efficacy of platinum(II) anticancer agents via overcoming their limitations.…”

Codelivery of satraplatin and aminopyrrolic receptor with Pluronic F127-based polyaniline nanoparticles with NIR induced release for combined chemotherapy

“…However, satraplatin shows the same anticancer mechanism as cisplatin by inducing the formation of nuclear DNA adducts to inhibit DNA replication, which might suffer the acquired drug resistance [19]. Traditional platinum anticancer agents lack selectivity of killing between cancer cells and normal cells [20,21]. Thus, improving the tumor selectivity of platinum complexes is crucial for mitigating their side effects.…”

Synthesis, characterization, and biological activity of new mixed ammine/amine platinum(IV) complexes

“…[4,5] New therapeutic approaches including combination medication, incorporation of targeting units into platinum(II) agents of known anticancer activity, and prodrug design have been explored to improve their pharmacological properties. [6][7][8][9] Among the metal pharmaceuticals in development, octahedral platinum(IV) complexes represent impetus to search for new antitumor platinum agents as they display a number of advantages related to their inertness and the possibility of modifying pharmacological properties through the addition of axial ligands. [4,10] It is widely accepted that platinum(IV) complexes act as prodrugs and release the active square planar platinum(II) centers by removing the axial ligands.…”