Anticancer, Biophysical and Computational Investigations of Half-Sandwich Ruthenium(II) Thiosemicarbazone Complexes: The Effect of Arene Versus Thiacrown Face-Cap

Authors

Floyd A. Beckford
Alyssa Stott
P. Canisius Mbarushimana
Marc-Andre Leblanc
Kinsey Hall
Samantha Smith
Jimmie L. Bullock
Dennis J. Houghton
Alvin A. Holder, Old Dominion UniversityFollow
Nikolay Gerasimchuk
Antonio Gonzalez-Sarrías

Document Type

Article

Publication Date

2016

DOI

10.15761/IJC.1000101

Publication Title

Interdisciplinary Journal of Chemistry

Volume

1

Issue

1

Pages

1-15

Abstract

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h⁶-p-cymene)Ru(dmabTSC)Cl]PF₆, [(h⁶-benzene)Ru(dmabTSC)Cl]PF₆ (arene complexes), and [([9]aneS₃(dmabTSC)Cl]PF₆ (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 10⁵ M^-1. In addition they all bind strongly to human serum albumin with binding constants between 10⁵ and 10⁶ M^-1. There appears to be a single binding site on the protein for these complexes. A computational investigation of these complexes and their hydrolysis products was carried out by molecular docking with DNA and topoisomerase II. From this analysis it is noted that the type of face-capping ligand had different effects on the two macromolecules. It is therefore noted that the knowledge gained from this study will be useful in identifying the type of complexes in this class that show useful metallodrug potential.

Rights

© 2016 Beckford FA.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Original Publication Citation

Beckford, F. A., Stott, A., Mbarushimana, P. C., LeBlanc, M.-A., Hall, K., Smith, S., Bullock, J. L., Houghton, D. L., Holder, A. A., Gerasimchuk, N., Gonzalez-Sarrías, A., & Seeram, N. (2016). Anticancer, biophysical and computational investigations of half-sandwich ruthenium (II) thiosemicarbazone complexes: The effect of arene versus thiacrown face-cap. Interdisciplinary Journal of Chemistry, 1(1), 1-15. https://doi.org/10.15761/IJC.1000101

ORCID

0000-0001-9618-5297 (Holder)

Repository Citation

Beckford, Floyd A.; Stott, Alyssa; Mbarushimana, P. Canisius; Leblanc, Marc-Andre; Hall, Kinsey; Smith, Samantha; Bullock, Jimmie L.; Houghton, Dennis J.; Holder, Alvin A.; Gerasimchuk, Nikolay; and Gonzalez-Sarrías, Antonio, "Anticancer, Biophysical and Computational Investigations of Half-Sandwich Ruthenium(II) Thiosemicarbazone Complexes: The Effect of Arene Versus Thiacrown Face-Cap" (2016). Chemistry & Biochemistry Faculty Publications. 241.
https://digitalcommons.odu.edu/chemistry_fac_pubs/241