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

Abstract

Two known tin-based polymers of formula {[R3Sn(CH3COO)]n} where R = n-Bu&ndash

(1) and R = Ph&ndash

(2),were evaluated for their in vitro biological properties. The compounds were characterized via their physical properties and FT-IR, 119Sn M&ouml

ssbauer, 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&ndash

Sn&ndash

O&middot

&middot

&middot

Sn&prime

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 &times

104 (1) and 7.3 &times

104 (2) M&minus

1 respectively. Finally, the type of DNA binding interactions with 1 and 2 was confirmed by docking studies.