Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes
2014
Autori:
Mijatović, SanjaBulatović, Mirna Z.
Mojić, Marija
Stošić-Grujičić, Stanislava
Miljković, Đorđe
Maksimović-Ivanić, Danijela
Gomez-Ruiz, Santiago
Pinkas, Jiri
Horacek, Michal
Kaluđerović, Goran N.
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
,
© 2013 Elsevier B.V.
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
The previously known complexes {[}Ti\{(Me2CMe2C)(eta(5)-C5H4)(2)\}Cl-2]
(1), {[}Ti\{Me2C(eta(5)-C5H4)(2)\}Cl-2] (2), {[}Ti
\{Me2Si(eta(5)-C5H4)(2)\}Cl-2] (4), {[}Ti\{MePhSi(eta(5)-C5H4)(2)\}Cl-2]
(5) and {[}Ti\{MePhSi(eta(5)-C5Me4)(2)\}Cl-2] (6) have been prepared
following reported procedures. The novel complex
{[}Ti\{MePhC(eta(5)-C5H4)(2)\}Cl-2] (3) has been prepared and
characterized. The cytotoxic activity of 1-6 has been tested after 72 h
on melanoma A375 and B16, prostate cancer DU145 and LNCaP and colon
cancer HCT116, SW620 and CT26CL25 cell lines observing a high cytotoxic
activity of complexes 1 and 6 compared to the reference compound
({[}Ti(eta(5)-C5H5)(2)\}Cl-2]). 1 and 6 have also been tested against
primary normal mouse keratinocytes and lung fibroblasts. While viability
of both type of primary cells was significantly less affected by 1 in
comparison to the reference compound {[}Ti(eta(5)-C5H5)(2)Cl-2],
compound 6 was completely nontoxic for nonmalignant cells, indicating a
potential selectivity of this compound towards cancer cell lines. In
addition CFSE staining, cell cycle analysis, AnnexinV-FITC/PI staining,
detection of caspase activity and mitochondrial potential showed that 1
and 6 were acting through inhibition of proliferation and subsequent
induction of mitochondrial dependent apoptosis in colon cancer cell
lines, HCT116 and SW620, which express low sensitivity to cisplatin.
Compound 6 was found to be the leading drug in this group since it shows
the fastest and most selective anticancer profile. (C) 2013 Elsevier
B.V. All rights reserved.
Ključne reči:
Titanocene derivatives; Cytotoxicity; Primary cells; Cell cycle analysis; Caspase detectionIzvor:
Journal of Organometallic Chemistry, 2014, 751, 361-367
DOI: 10.1016/j.jorganchem.2013.07.059
ISSN: 1872-8561