79055 20200716101430.0 doi 10.1002/cmdc.201800796 sideral 111550 ART-2019-111550 eng Curado, N. Preparation of Titanocene–Gold Compounds Based on Highly Active Gold(I)-N-Heterocyclic Carbene Anticancer Agents: Preliminary in vitro Studies in Renal and Prostate Cancer Cell Lines 2019 Access copy available to the general public Unrestricted Heterometallic titanocene-based compounds containing gold(I)-phosphane fragments have been extremely successful against renal cancer in vitro and in vivo. The exchange of phosphane by N-heterocyclic carbene ligands to improve or modulate their pharmacological profile afforded bimetallic complexes effective against prostate cancer, but less effective against renal cancer in vitro. Herein we report the synthesis of new bimetallic Ti–Au compounds by the incorporation of two previously reported highly active gold(I)-N-heterocyclic carbene fragments derived from 4, 5-diarylimidazoles. The two new compounds [(¿ 5 -C 5 H 5 ) 2 TiMe(µ-mba)Au(NHC)] (where NHC=1, 3-dibenzyl-4, 5-diphenylimidazol-2-ylidene, NHC-Bn 2 a; or 1, 3-diethyl-4, 5-diphenylimidazol-2-ylidene, NHC-Et 2 b) with the dual linker (-OC(O)-p-C 6 H 4 -S-) containing both a carboxylate and a thiolate group were evaluated in vitro against renal and prostate cancer cell lines. The compounds were found to be more cytotoxic than previously described Ti–Au compounds containing non-optimized gold(I)-N-heterocyclic fragments. We present studies to evaluate their effects on cell death pathways, migration, inhibition of thioredoxin reductase (TrxR) and vascular endothelial growth factor (VEGF) in the PC3 prostate cancer cell line. The results show that the incorporation of a second metallic fragment such as titanocene into biologically active gold(I) compounds improves their pharmacological profile. info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 3.124 2019 0.895 2019 PHARMACOLOGY & PHARMACY 102 / 270 = 0.378 2019 Q2 T2 Drug Discovery 2019 Q1 CHEMISTRY, MEDICINAL 25 / 61 = 0.41 2019 Q2 T2 Organic Chemistry 2019 Q1 Pharmacology, Toxicology and Pharmaceutics (miscellaneous) 2019 Q1 Pharmacology 2019 Q2 Biochemistry 2019 Q2 Molecular Medicine 2019 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Giménez, N. Miachin, K. (orcid)0000-0001-9219-5420 Aliaga-Lavrijsen, M. Cornejo, M.A. Jarzecki, A.A. Contel, M. 14 (2019), 1-11 ChemMedChem ChemMedChem 1860-7179 728211 http://zaguan.unizar.es/record/79055/files/texto_completo.pdf Postprint 21029 http://zaguan.unizar.es/record/79055/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:79055 articulos driver 2020-07-16-08:49:12 ARTICLE