Synthesis of Pt(II) complexes of the type [Pt(1,10-phenanthroline)(SArFn)2] (SArFn = SC6H3-3,4-F2; SC6F4-4-H; SC6F5). Preliminary evaluation of their in vitro anticancer activity

J Inorg Biochem. 2020 Oct:211:111206. doi: 10.1016/j.jinorgbio.2020.111206. Epub 2020 Jul 25.

Abstract

A series of Pt(II) complexes of the type [Pt(1,10-phenanthroline)(SArFn)2] (SArFn = SC6H3-3,4-F2(1); SC6F4-4-H (2); SC6F5(3)) were synthesized from [Pt(1,10-phenanthroline)(Cl)2] and [Pb(SArFn)2] via metathesis reactions. The complexes were fully characterized including the unambiguous determination of their molecular structures by single-crystal X-ray diffraction techniques, showing the metal centers to be into a slightly distorted square-planar environments. The in vitro cytotoxic activity of the complexes was evaluated on six cancerous cell lines, i.e: glial cells of nervous central system (U-251), prostate (PC-3), leukemia (K-562), colon (HCT-15), breast (MCF-7) and lung (SKLU-1); we also included a healthy cell line of COS-7 (African green monkey kidney) for comparative purposes. We found that complex 2 was selective for PC-3. In addition, the IC50 values for the series of complexes were determined using the U-251, HCT-15 and SKLU-1 cancerous cell lines, as well as in the healthy cell line (COS-7), where complex 1 exhibited the best activity, with IC50 values going from 4.56 to 4.78 μM. These studies where further complemented with DNA docking theoretical calculations and DNA affinity experiments.

Keywords: Cancer; Coordination compounds; Docking; Fluorinated thiophenolates; Non-covalent interactions; Platinum complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray / methods
  • Humans
  • In Vitro Techniques
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Phenanthrolines / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Organoplatinum Compounds
  • Phenanthrolines
  • Cisplatin
  • 1,10-phenanthroline