Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes

0424576 - ÚFCH JH 2015 RIV CH eng J - Článek v odborném periodiku
Mijatović, S. - Bulatović, M. - Mojić, M. - Stošić-Grujičić, S. - Miljković, D. - Maksimović-Ivanić, D. - Gómez-Ruiz, S. - Pinkas, Jiří - Horáček, Michal - Kaluderović, G. N.
Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes.
Journal of Organometallic Chemistry. Roč. 751, FEB 2014 (2014), s. 361-367. ISSN 0022-328X. E-ISSN 1872-8561
Grant CEP: GA ČR(CZ) GAP207/12/2368
Institucionální podpora: RVO:61388955
Klíčová slova: titanocene derivatives * cytotoxicity * primary cells
Kód oboru RIV: CF - Fyzikální chemie a teoretická chemie
Impakt faktor: 2.173, rok: 2014

The previously known complexes [Ti{(Me2CMe2C)(η5-C5H4)2}Cl2] (1), [Ti{Me2C(η5-C5H4)2}Cl2] (2), [Ti{Me2Si(η5-C5H4)2}Cl2] (4), [Ti{MePhSi(η5-C5H4)2}Cl2] (5) and [Ti{MePhSi(η5-C5Me4)2}Cl2] (6) have been prepared following reported procedures. The novel complex [Ti{MePhC(η5-C5H4)2}Cl2] (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(η5-C5H5)2}Cl2]). 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(η5-C5H5)2Cl2], 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.
Trvalý link: http://hdl.handle.net/11104/0230640