Poly Organotin Acetates against DNA with Possible Implementation on Human Breast Cancer

Int J Mol Sci. 2018 Jul 14;19(7):2055. doi: 10.3390/ijms19072055.

Abstract

Two known tin-based polymers of formula {[R₃Sn(CH₃COO)]n} where R = n-Bu⁻ (1) and R = Ph⁻ (2),were evaluated for their in vitro biological properties. The compounds were characterized via their physical properties and FT-IR, 119Sn Mössbauer, and ¹H NMR spectroscopic data. The molecular structures were confirmed by single-crystal X-Ray diffraction crystallography. The geometry around the tin(IV) ion is trigonal bi-pyramidal. Variations in O⁻Sn⁻O···Sn' torsion angles lead to zig-zag and helical supramolecular assemblies for 1 and 2, respectively. The in vitro cell viability against human breast adenocarcinoma cancer cell lines: MCF-7 positive to estrogens receptors (ERs) and MDA-MB-231 negative to ERs upon their incubation with 1 and 2 was investigated. Their toxicity has been studied against normal human fetal lung fibroblast cells (MRC-5). Compounds 1 and 2 exhibit 134 and 223-fold respectively stronger antiproliferative activity against MDA-MB-231 than cisplatin. The type of the cell death caused by 1 or 2 was also determined using flow cytometry assay. The binding affinity of 1 and 2 towards the CT-DNA was suspected from the differentiation of the viscosity which occurred in the solution containing increasing amounts of 1 and 2. Changes in fluorescent emission light of Ethidium bromide (EB) in the presence of DNA confirmed the intercalation mode of interactions into DNA of both complexes 1 and 2 which have been ascertained from viscosity measurements. The corresponding apparent binding constants (Kapp) of 1 and 2 towards CT-DNA calculated through fluorescence spectra are 4.9 × 10⁴ (1) and 7.3 × 10⁴ (2) M-1 respectively. Finally, the type of DNA binding interactions with 1 and 2 was confirmed by docking studies.

Keywords: acetic acid; anti-cancer activity; bio-polymer; biological inorganic chemistry; cell cycle; organotins.

MeSH terms

  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA / chemistry*
  • DNA / metabolism
  • Humans
  • MCF-7 Cells
  • Molecular Docking Simulation*
  • Nucleic Acid Conformation*
  • Organotin Compounds / chemistry*
  • Organotin Compounds / metabolism
  • Organotin Compounds / pharmacology

Substances

  • Organotin Compounds
  • DNA