Terpyridyl oxovanadium(IV) complexes for DNA crosslinking and mito-targeted photocytotoxicity

Arun Kumar; Ila Pant; Akanksha Dixit; Samya Banerjee; Bhabatosh Banik; Rupak Saha; Paturu Kondaiah; Akhil R Chakravarty

doi:10.1016/j.jinorgbio.2017.05.015

Terpyridyl oxovanadium(IV) complexes for DNA crosslinking and mito-targeted photocytotoxicity

J Inorg Biochem. 2017 Sep:174:45-54. doi: 10.1016/j.jinorgbio.2017.05.015. Epub 2017 May 30.

Authors

Arun Kumar¹, Ila Pant², Akanksha Dixit³, Samya Banerjee¹, Bhabatosh Banik¹, Rupak Saha¹, Paturu Kondaiah⁴, Akhil R Chakravarty⁵

Affiliations

¹ Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560 012, India.
² Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560 012, India.
³ Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
⁴ Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560 012, India. Electronic address: paturu@mrdg.iisc.ernet.in.
⁵ Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560 012, India. Electronic address: arc@ipc.iisc.ernet.in.

PMID: 28601723
DOI: 10.1016/j.jinorgbio.2017.05.015

Abstract

Oxovanadium(IV) complexes [VO(L¹/L²)Cl₂]ⁿ⁺ (1,2) of (anthracenyl)terpyridine (An-tpy as L¹ in 1, n=0) and triphenylphosphonium-appended (anthracenyl)terpyridine (An-tpy-TPP⁺ as L² in 2, n=1) were synthesized, characterized and their DNA crosslinking ability, photocytotoxicity in visible light and cellular localization in cancer cells studied. The bromide derivative of 2, viz. [VO(An-tpy-TPP)Br₂]Br (3) is structurally characterized. The structure showed trans disposition of two halides in the coordination sphere and the TPP⁺ unit is a pendant to the terpyridyl ligand. The DNA melting and comet assay studies on the complexes suggest the formation of DNA crosslinks. Complexes 1 and 2 displayed ~10 fold increase in cytotoxicity on exposure to visible light (400-700nm) when compared to those in dark in HeLa and MCF-7 cells. FACScan (Fluorescence Associated Cell Sorter Scan) analysis showed cellular apoptosis when treated with the complex in visible light in comparison to their dark controls. Fluorescence microscopic studies using complex 2 revealed its mitochondrial localization within the cancer cells.

Keywords: Crystal structure; DNA crosslinking; Mitochondria targeting; Photocytotoxicity; Terpyridine derivative; Vanadium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anthracenes* / chemical synthesis
Anthracenes* / chemistry
Anthracenes* / pharmacology
Apoptosis / drug effects
Cross-Linking Reagents* / chemical synthesis
Cross-Linking Reagents* / chemistry
Cross-Linking Reagents* / pharmacology
DNA, Neoplasm / metabolism*
HeLa Cells
Humans
Mitochondria / metabolism
Mitochondria / pathology
Neoplasms / drug therapy*
Neoplasms / metabolism
Neoplasms / pathology
Phototherapy*
Vanadates* / chemical synthesis
Vanadates* / chemistry
Vanadates* / pharmacology

Substances

Anthracenes
Cross-Linking Reagents
DNA, Neoplasm
oxovanadium IV
Vanadates