New Platinum (II) Ternary Complexes of Formamidine and Pyrophosphate: Synthesis, Characterization and DFT Calculations and In vitro Cytotoxicity

Comb Chem High Throughput Screen. 2020;23(7):611-623. doi: 10.2174/1386207323666200218115700.

Abstract

Aim and objective: Platinum (II) and platinum (IV) of pyrophosphate complexes have been prepared and characterized to discover their potential as antitumor drugs. This study was conducted to prepare and characterize new ternary platinum (II) complexes with formamidine and pyrophosphate as an antitumor candidate.

Materials and methods: The complexes have been characterized by mass, infrared, UV-Vis. spectroscopy, elemental analysis, magnetic susceptibility, thermal analyses, and theoretical calculations. They have been tested for their cytotoxicity, which was carried out using the fastcolorimetric assay for cellular growth and survival against MCF-7 (breast cancer cell line), HCT- 116 (colon carcinoma cell line), and HepG-2 (hepatocellular cancer cell line).

Results: All complexes are diamagnetic, and the electronic spectral data displayed the bands due to square planar Pt(II) complexes. The optimized complexes structures (1-4) indicated a distorted square planar geometry where O-Pt-O and N-Pt-N bond angles were 82.04°-96.44°, respectively. Results also show that all complexes are neutral, stable and non-hygroscopic and have noticeable cytotoxicity with IC50 (μM): 0.035-0.144 MCF-7(breast cancer cell line), 0.042-0.187 HCT-116 (colon carcinoma cell line), and 0.063-0.168 HepG-2 (hepatocellular cancer cell line). Moreover, the results show that the complex (4) has the best IC50 value.

Conclusion: The complexes showed noticeable cytotoxicity and are considered as promising antitumor candidates for further applications.

Keywords: Pt(II); antitumor; formamidine; magnetic and MO calculations; pyrophosphate; spectroscopy; thermal analysis.

MeSH terms

  • Amidines / chemistry
  • Amidines / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Density Functional Theory*
  • Diphosphates / chemistry
  • Diphosphates / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Platinum / chemistry
  • Platinum / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Amidines
  • Antineoplastic Agents
  • Coordination Complexes
  • Diphosphates
  • formamidine
  • Platinum