000086432 001__ 86432
000086432 005__ 20200716101440.0
000086432 0247_ $$2doi$$a10.1016/j.jorganchem.2018.12.011
000086432 0248_ $$2sideral$$a109712
000086432 037__ $$aART-2019-109712
000086432 041__ $$aeng
000086432 100__ $$ade la Cueva-Alique, I.
000086432 245__ $$aStudy of the anticancer properties of optically active titanocene oximato compounds
000086432 260__ $$c2019
000086432 5060_ $$aAccess copy available to the general public$$fUnrestricted
000086432 5203_ $$aNew 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.
000086432 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/CTQ2014-58270-R
000086432 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000086432 590__ $$a2.304$$b2019
000086432 592__ $$a0.506$$b2019
000086432 591__ $$aCHEMISTRY, ORGANIC$$b26 / 57 = 0.456$$c2019$$dQ2$$eT2
000086432 593__ $$aMaterials Chemistry$$c2019$$dQ2
000086432 591__ $$aCHEMISTRY, INORGANIC & NUCLEAR$$b20 / 45 = 0.444$$c2019$$dQ2$$eT2
000086432 593__ $$aInorganic Chemistry$$c2019$$dQ2
000086432 593__ $$aPhysical and Theoretical Chemistry$$c2019$$dQ2
000086432 593__ $$aOrganic Chemistry$$c2019$$dQ2
000086432 593__ $$aBiochemistry$$c2019$$dQ3
000086432 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000086432 700__ $$aSierra, S.
000086432 700__ $$aPérez-Redondo, A.
000086432 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, I.$$uUniversidad de Zaragoza
000086432 700__ $$aGude, L.
000086432 700__ $$aCuenca, T.
000086432 700__ $$aRoyo, E.
000086432 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000086432 773__ $$g881 (2019), 150-158$$pJ. organomet. chem.$$tJournal of Organometallic Chemistry$$x0022-328X
000086432 8564_ $$s354200$$uhttps://zaguan.unizar.es/record/86432/files/texto_completo.pdf$$yPostprint
000086432 8564_ $$s193440$$uhttps://zaguan.unizar.es/record/86432/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000086432 909CO $$ooai:zaguan.unizar.es:86432$$particulos$$pdriver
000086432 951__ $$a2020-07-16-08:58:02
000086432 980__ $$aARTICLE