@article{
author = "Ceballos-Torres, Jesus and del Hierro, Isabel and Prashar, Sanjiv and Fajardo, Mariano and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Kaluđerović, Goran N. and Gomez-Ruiz, Santiago",
year = "2014",
abstract = "Four alkenyl-substituted titanocene dichloride complexes
{[}Ti(eta(5)-C5H5)\{eta(5)-C5H4(CMeR(CH2CH2CH=CH2))\}Cl-2] (R = Me (8),
Ph (9)) and
{[}Ti(eta(5)-C5H5)\{eta(5)-C5H3(CMeR(CH2CH2CH=CH2))(SiMe3)\}] (R = Me
(10), Ph (11)) have been synthesized and characterized.
The cytotoxic activity of 8-11 has been tested against human tumour cell
lines from four different tissue origins {[}8505C (anaplastic thyroid
cancer), DLD-1 (colon cancer), FaDu (head and neck cancer), A2780
(ovarian cancer) and A549 (lung carcinoma)] and compared with those of
the reference complexes {[}Ti(eta(5)-C5H5)(2)Cl-2] and cisplatin. The
majority of the studied titanocene compounds are more active than the
reference complex {[}Ti(eta(5)-C5H5)(2)Cl-2] indicating that the
presence of alkenyl substituents leads to an increase in the cytotoxic
activity. In addition, the presence of a trimethylsilyl group on the
cyclopentadienyl ring also leads to an increase in the cytotoxic
activity of 10 with respect to 8. The contrary is observed for 9 and 11
(except on the DLD-1 cell line) with 9 (without -SiMe3) being more
active than 11 (with -SiMe3). However, all synthesized complexes,
exhibited lower cytotoxic activity than cisplatin.
Stability and binding studies based on cyclic voltammetry and UV-visible
spectroscopy have been carried out in order to explore possible
interactions between titanocene derivatives and various intracellular
molecules, such as the nitrogenous bases cytosine and thymine, the
nucleotides adenosine and guanosine, and single-strand fish sperm DNA
(FS-DNA). These experiments have allowed us to construct models to
examine the interactions and action mechanisms of titanocene complexes
inside the cells. In addition, this is one of the first studies on the
interactions of titanocene derivatives with DNA fragments using cyclic
voltammetry. (c) 2014 Elsevier B.V. All rights reserved.",
journal = "Journal of Organometallic Chemistry",
title = "Alkenyl-substituted titanocene dichloride complexes: Stability studies,
binding and cytotoxicity",
volume = "769",
doi = "10.1016/j.jorganchem.2014.06.031",
pages = "46-57"
}