86432 20200716101440.0 doi 10.1016/j.jorganchem.2018.12.011 sideral 109712 ART-2019-109712 eng de la Cueva-Alique, I. Study of the anticancer properties of optically active titanocene oximato compounds 2019 Access copy available to the general public Unrestricted New water soluble and optically active cyclopentadienyl titanium derivatives [(¿5-C5H5)2Ti{(1R, 4S)-¿ON, (R)NH}Cl] (R = Bn (Benzyl) 1a’, 2-pic (2-picolylamine) 1b’) have been synthesized. The novel compounds along with those previously described [(¿5-C5H5)2Ti{(1S, 4R)-¿ON, (R)NH}Cl] (R = Bn 1a, 2-pic 1b) were evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of 1b was determined by single crystal X-ray crystallography and showed a unique terminal monohapto Ti–O disposition of the oximato ligand. All enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3 and DU-145, lung A-549, pancreas MiaPaca-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. In addition, 1a, 1b and 1b’ were tested against non-tumorigenic prostate RWPE-1 cell line. After 24 h of incubation, 1b and 1b’ were moderately active against Jurkat and A-549 cells. The anti-proliferative effect of titanium compounds on prostate PC-3, DU-145 and RWPE-1 cell lines was also assessed after 72 h of drug exposure. The cytotoxic profile of the enantiomers was similar, exception made for the PC-3 cells, with S, R-isomers exhibiting cytotoxicities 2 to 3 times higher than R, S-compounds. Under these conditions, derivative 1b showed calculated IC50 values better than those of Tacke''s Titanocene-Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride) on both the prostate PC-3 and DU-145 cells. 1a and 1b cytotoxic behaviour shows certain selectiveness, with activities 2–4 times lower on normal prostate RWPE-1 than on cancer PC-3 cells. Furthermore, 1b produces higher cytotoxicity on prostate PC-3, DU-145 and RWPE-1 cells than the additive dose of titanocene dichloride and pro-ligand b·HCl. Additionally, compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, which suggest that these metal complexes and/or their hydrolysis products bind DNA either in the minor groove or externally. info:eu-repo/grantAgreement/ES/MICINN/CTQ2014-58270-R info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 2.304 2019 0.506 2019 CHEMISTRY, ORGANIC 26 / 57 = 0.456 2019 Q2 T2 Materials Chemistry 2019 Q2 CHEMISTRY, INORGANIC & NUCLEAR 20 / 45 = 0.444 2019 Q2 T2 Inorganic Chemistry 2019 Q2 Physical and Theoretical Chemistry 2019 Q2 Organic Chemistry 2019 Q2 Biochemistry 2019 Q3 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Sierra, S. Pérez-Redondo, A. (orcid)0000-0002-2315-9079 Marzo, I. Universidad de Zaragoza Gude, L. Cuenca, T. Royo, E. 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 881 (2019), 150-158 J. organomet. chem. Journal of Organometallic Chemistry 0022-328X 354200 http://zaguan.unizar.es/record/86432/files/texto_completo.pdf Postprint 193440 http://zaguan.unizar.es/record/86432/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:86432 articulos driver 2020-07-16-08:58:02 ARTICLE