Endoplasmic reticulum targeting tumour selective photocytotoxic oxovanadium(IV) complexes having vitamin-B6 and acridinyl moieties

Dalton Trans. 2016 Jan 14;45(2):783-96. doi: 10.1039/c5dt03412d.

Abstract

Oxovanadium(iv) complexes of vitamin-B6 Schiff base, viz., [VO(HL(1)/L(2)/L(3))(B)]Cl (), where B is 2,2'-bipyridine (bpy in and ), 11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine (acdppz in and ), H2L(1)·HCl is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-1-ium chloride (in and ), HL(2) is 2-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)phenol (in ) and HL(3) is 4-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in ) were synthesized, characterized and their cellular uptake, photo-activated cytotoxicity and intracellular localization were studied. Complexes , as the perchlorate salt of , and , as the hexafluorophosphate salt of , were structurally characterized. Vitamin-B6 transporting membrane carrier (VTC) mediated entry into tumour cells in preference to the normal ones seems to be responsible for the higher cellular uptake of the complexes into HeLa and MCF-7 cells over MCF-10A cells. Complexes and having acdppz as the photosensitizer exhibit remarkable photocytotoxicity in these cancer cells giving IC50 of <0.9 μM. The complexes remain non-toxic in the dark. The complexes show photo-induced apoptotic cell death via singlet oxygen ((1)O2) generation. Fluorescence microscopy reveals specific localization of complex to endoplasmic reticulum (ER) and generation of (1)O2 possibly leads to apoptotic cell death by triggering ER stress response (ERSR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / chemistry
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • HeLa Cells
  • Humans
  • Light
  • MCF-7 Cells
  • Microscopy, Fluorescence
  • Molecular Conformation
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / pharmacology
  • Quantum Theory
  • Schiff Bases / chemistry
  • Singlet Oxygen / metabolism
  • Solubility
  • Vanadates / chemistry*
  • Vitamin B 6 / chemistry*

Substances

  • Coordination Complexes
  • Photosensitizing Agents
  • Schiff Bases
  • Singlet Oxygen
  • Vanadates
  • 2,2'-Dipyridyl
  • Vitamin B 6