Sulfonated Schiff base Sn(IV) complexes as potential anticancer agents

J Inorg Biochem. 2016 Sep:162:83-95. doi: 10.1016/j.jinorgbio.2016.06.008. Epub 2016 Jun 8.

Abstract

Syntheses, crystal structures and biological activities of the diphenoxo-bridged diorgano dinuclear Sn(IV) compounds [Sn(Et)2(HL)(H2O)]2 (1) and [Sn(n-Bu)2(HL)(H2O)]2 (2) derived from the Schiff base 2-[(2,3-dihydroxyphenyl)methylideneamino]benzenesulfonic acid trihydrate (H3L·3H2O) are described. The monoprotonated form (HL2-) of the Schiff base behaves as O,O'-bidentate ligand, chelating the metal by the two phenoxo oxygen atoms. The hexacoordinated metal centres in 1 and 2 are bridged by a phenoxo oxygen and the remaining coordination positions are fulfilled by the other phenoxo oxygen, two organic groups (ethyl for 1 and n-butyl for 2) and a water molecule. A two dimensional zigzag sheet in 1 and three dimensional polymeric networks in H3L·3H2O and 2 are stabilized by a number of non-covalent, H-bonding and π⋯π stacking interactions. The DNA binding activities of these complexes have been studied by UV-vis and fluorescence spectroscopies. Their antiproliferative efficacies have been evaluated on A-549, HeLa and MDA-MB-231 cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. IC50 values (1.35±0.23, 2.43±0.54 and 1.74±0.04μM for 2) are indicative of a substantial cytotoxicity of 2, mainly towards the A-549 lung cancer cell line. The greater antiproliferative efficacy of 2has further been studied by fluorescence activated cell sorting (FACS) and nuclear morphology by Hoechst/propidium iodide (PI) double staining method. The possible mode of the apoptotic pathway for 2has been substantiated by the reactive oxygen species (ROS) generation studies.

Keywords: Cytotoxicity in vitro; DNA binding; Diorgano dinuclear Sn(IV); Reactive oxygen species; Sulfonated Schiff base.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Benzenesulfonates / chemistry*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / pharmacology
  • DNA / chemistry
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Molecular Conformation
  • Organotin Compounds / chemical synthesis*
  • Organotin Compounds / pharmacology
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism
  • Schiff Bases / chemistry*
  • Structure-Activity Relationship
  • Tin / chemistry*

Substances

  • Antineoplastic Agents
  • Benzenesulfonates
  • Coordination Complexes
  • Organotin Compounds
  • Reactive Oxygen Species
  • Schiff Bases
  • Tin
  • DNA
  • calf thymus DNA