Iridium(III) coordination of N(6) modified adenine derivatives with aminoacid chains

J Inorg Biochem. 2020 Apr;205:111000. doi: 10.1016/j.jinorgbio.2020.111000. Epub 2020 Jan 18.

Abstract

In this manuscript we report the preparation of three N6-aminoacid-adenine-derivatives: N-(7H-purin-6-yl)glycine·0.5H2O (N6-GlyAde), N-(7H-purin-6-yl)-β-alanine·1.5H2O (N6-β-AlaAde) and N-(7H-purin-6-yl)-γ-aminobutyric·2H2O (N6-GabaAde) and the synthesis and X-ray characterization of three Ir(III) NAMI-A derivatives (NAMI-A is [imidazoleH][trans-RuIIICl4(DMSO-κS)(imidazole)]) [trans-IrIIICl4(DMSO-κS)(N3-H)-(7H-purin-6-yl)glycine-κN9] (1), [trans-IrIIICl4(DMSO-κS)(N3-H)-(7H-purin-6-yl)-β-alanine-κN9] hydrate (2) and [trans-IrIIICl4(DMSO-κS)(N3-H)-(7H-purin-6-yl)-γ-aminobutyryl-κN9] (3). In all complexes the metal center shows octahedral geometry with coordination to four chlorido ligands and one S coordinated dimethylsulfoxide (DMSO-κS). The coordination sphere of the metal is completed by the modified adenine molecule which is bound via N(9) and protonated at N(3). In two complexes the importance of lone pair (lp)-π interactions involving the adenine ring have been studied using density functional theory (DFT) calculations and the Bader's theory of atoms in molecules. Furthermore, the ability of complexes (1-3) to affect the cell viability was evaluated against three different cancer cell lines: human lung carcinoma cells (A549), human cervical carcinoma cells (HeLa) and human breast cancer cells (MCF7). We have also analyzed their ability to cleave the DNA experimentally and their affinity for two models of DNA has been studied using molecular docking simulations.

Keywords: Adenine-Gaba; Adenine-β-alanine; Docking; Ir(III); N(6)-modified-aminoacid adenine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenine* / analogs & derivatives
  • Adenine* / chemistry
  • Adenine* / pharmacology
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • HeLa Cells
  • Humans
  • Iridium* / chemistry
  • Iridium* / pharmacology
  • MCF-7 Cells
  • Molecular Docking Simulation*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Iridium
  • Adenine