Synthesis, antiradical activity and in vitro cytotoxicity of novel organotin complexes based on 2,6-di-tert-butyl-4-mercaptophenol

Abstract

A series of organotin complexes with Sn-S bonds of formulae Me2Sn(SR)2 (1); Et2Sn(SR)2 (2); (n-Bu)2Sn(SR)2 (3); Ph2Sn(SR)2 (4); R2Sn(SR)2 (5); Me3SnSR (6); Ph3SnSR (7) (R = 3,5-di-tert-butyl-4-hydroxyphenyl) were synthesized and characterized by elemental analysis, (1)H, (13)C NMR, and IR. The crystal structures of compounds 1, 4, 5, and 7 were determined by X-ray diffraction analysis. The tetrahedral geometry around the Sn center in the monocrystals of 1, 4, 5, and 7 was confirmed by X-ray crystallography. The high radical scavenging activity of the complexes was confirmed spectrophotometrically in a DPPH-test. The binding affinity of 1-7 and the starting R2SnCl2 (8) towards tubulin through their interaction with SH groups of proteins was studied. It was found that the hindered organotin complexes could interact with the colchicine site of tubulin, which makes them promising antimitotic drugs. Compounds 1-8 were tested for their in vitro cytotoxicity against human breast (MCF-7) and human cervix (HeLa) adenocarcinoma cells. Complexes 1-8 were also tested against normal human fetal lung fibroblast cells (MRC-5). Complexes 2-4 and 8 exhibit significantly lower cytostatic activity against the normal MRC-5 cell line compared to the tumor cell lines MCF-7 and HeLa used. A high activity against both cell lines 250 nM (MCF-7) and 160 nM (HeLa) was determined for the triphenyltin complex 7 while the introduction of hindered phenol groups decreases the cytotoxicity of the complexes against normal cells.

Triphenyltin recognition by primary structures of effector proteins and the protein network of Bacillus thuringiensis during the triphenyltin degradation process

“…Although it was deduced that tin atoms of TPT react with free sulfhydryl groups in proteins 15 and that TPT induces conformational changes of albumin by hydrophobic forces and forms TPT-albumin complexes 16 , those conclusions were inferred through experiments using active cells but not through direct evidence of interactions between proteins and TPT. Based on functional analysis in the STRING and NCBI databases, most of the proteins interacting with TPT were involved in carbon source, amino acid, fatty acid and energy metabolism; redox processes; and protein synthesis (Supplementary Tables 2–4.…”

Antioxidative vs cytotoxic activities of organotin complexes bearing 2,6‐di‐tert‐butylphenol moieties

“…Synthesis of complexes 1–7 from 2,6‐di‐ tert ‐butyl‐4‐mercaptophenol ( L 1 S H) has been reported by us . Starting Schiff base 2‐(N‐3 ′ ,5 ′ ‐di‐ tert ‐butyl‐4 ′ ‐hydroxyphenyl)‐iminomethylphenol ( L 2 ) was prepared as described previously .…”

“…The chelating ligands bearing 2,6‐di‐ tert ‐butylphenol pendant were proposed for neutralisation of non‐specific toxicity of organotins . We have recently published the synthesis, antioxidant and cytotoxic properties of organotin thiolates Me 2 Sn(L 1 S) 2 ( 1, L 1 = 3,5‐di‐ tert ‐butyl‐4‐hydroxyphenyl); Et 2 Sn(L 1 S) 2 ( 2 ); Bu 2 Sn(L 1 S) 2 ( 3 ); Ph 2 Sn(L 1 S) 2 ( 4 ); (L 1 ) 2 Sn(L 1 S) 2 ( 5 ); Me 3 Sn(L 1 S) ( 6 ) Ph 3 Sn(L 1 S) ( 7 ) on the base of 2,6‐di‐ tert ‐butyl‐4‐mercaptophenol ( L 1 SH ) . In order to establish possible mechanisms of their cytotoxicity the interaction with tubulin as molecular target and molecular docking were explored.…”

“…This mode of action may be among the reasons of their cytotoxicity, but the mechanism could not be explained based solely on these data. Cytotoxicity of compounds was determined on human cancer cells lines (MCF‐7, HeLa) and normal human fetal lung fibroblast cells (MRC‐5) in vitro . Complexes 2–4 exhibited lower cytostatic activity against the normal MRC‐5 cell line compared to the tumour cell lines MCF‐7 and HeLa.…”

In vitro antimicrobial activity of two dibutyltin(IV) complexes of kaurenic acids derivatives

“…It is noteworthy, the cell apoptosis induction by Sn metal (Shpakovsky et al, 2014); the anti-microbial activity is also known, and has been reported as a pesticide against the flour red scarab or Tribolium casteneum (Win et al, 2012;Kumar and Pankaj, 2014). However, of all the biological activities tried for organotin(IV) compounds, the most noteworthy is the anti-tumoral activity (Sedaghat et al, 2013;Nath et al, 2003 …”