Organotin(IV) complexes derived from Schiff base N'-[(1E)-(2-hydroxy-3-methoxyphenyl)methylidene]pyridine-4-carbohydrazone: synthesis, in vitro cytotoxicities and DNA/BSA interaction.

Abstract

Five organotin(IV) compounds were synthesized from N'-[(1E)-(2-hydroxy-3-methoxyphenyl)methylidene]pyridine-4-carbohydrazone and the corresponding dialkyltin(IV) or trialkyltin(IV) precursor. Solid state structures were determined by IR, elemental analysis, NMR spectroscopy, and for 1, 2, 4 and 5 single crystal X-ray diffraction analysis. Compounds 1, 2 and 4 are monomers with the tin atoms five-coordinated in distorted trigonal bipyramid, of which the deprotonated Schiff base ligand chelate to tin center in the enolic tridentate mode. Differently, in compound 5, the enolization does not occur for the Schiff base ligand, and only the pyridinyl N atom and the deprotonated phenol hydroxyl oxygen atom participate in the coordination. Fascinatingly, six trimethyltin(IV) coordination units are linked by the Sn⋯N weak interaction atoms and form a 72-membered crown-like macrocycle. Preliminary in vitro cytotoxicity studies on five human tumor cells lines (HL-60, A549, HT-29, HCT-116 and Caco-2) by MTT assay reveal that di-n-butyltin(IV) complex 2 and diphenyltin(IV) complex 4 triggered significant antiproliferative effects in cultured tumor cells, and their cytotoxic activity correlates with intracellular organotin(IV) concentration. The interaction of the complexes with calf thymus DNA (CT-DNA) has been explored by absorption and emission titration methods, which revealed that complexes 2 and 4 interact with CT-DNA through groove-binding and partial intercalation of the extended planar ligand with the DNA base stack. Further, the albumin interactions of complexes 2 and 4 were investigated using fluorescence quenching spectra and synchronous fluorescence spectra. Studies reveal that di-n-butyltin(IV) complex 2 with higher cytotoxicity show stronger DNA/BSA interaction than diphenyltin(IV) complex 4.

• Authors: Min Hong, Honglin Geng, Meiju Niu, Fei Wang, Dacheng Li, Jifeng Liu, Handong Yin
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 86 Pg. 550-61 (Oct 30 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 25216377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Hydrazones
• N'-((1E)-(2-hydroxy-3-methoxyphenyl)methylidene)pyridine-4-carbohydrazone
• Organotin Compounds
• Pyridines
• Schiff Bases
• Serum Albumin, Bovine
• DNA
• calf thymus DNA

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Caco-2 Cells
• Cell Proliferation (drug effects)
• DNA (chemistry)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HCT116 Cells
• HL-60 Cells
• HT29 Cells
• Humans
• Hydrazones (chemistry)
• Models, Molecular
• Molecular Structure
• Organotin Compounds (chemical synthesis, chemistry, pharmacology)
• Pyridines (chemistry)
• Schiff Bases (chemistry)
• Serum Albumin, Bovine (chemistry)
• Structure-Activity Relationship
• Tumor Cells, Cultured