000079055 001__ 79055 000079055 005__ 20200716101430.0 000079055 0247_ $$2doi$$a10.1002/cmdc.201800796 000079055 0248_ $$2sideral$$a111550 000079055 037__ $$aART-2019-111550 000079055 041__ $$aeng 000079055 100__ $$aCurado, N. 000079055 245__ $$aPreparation 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 000079055 260__ $$c2019 000079055 5060_ $$aAccess copy available to the general public$$fUnrestricted 000079055 5203_ $$aHeterometallic 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. 000079055 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000079055 590__ $$a3.124$$b2019 000079055 592__ $$a0.895$$b2019 000079055 591__ $$aPHARMACOLOGY & PHARMACY$$b102 / 270 = 0.378$$c2019$$dQ2$$eT2 000079055 593__ $$aDrug Discovery$$c2019$$dQ1 000079055 591__ $$aCHEMISTRY, MEDICINAL$$b25 / 61 = 0.41$$c2019$$dQ2$$eT2 000079055 593__ $$aOrganic Chemistry$$c2019$$dQ1 000079055 593__ $$aPharmacology, Toxicology and Pharmaceutics (miscellaneous)$$c2019$$dQ1 000079055 593__ $$aPharmacology$$c2019$$dQ2 000079055 593__ $$aBiochemistry$$c2019$$dQ2 000079055 593__ $$aMolecular Medicine$$c2019$$dQ2 000079055 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000079055 700__ $$aGiménez, N. 000079055 700__ $$aMiachin, K. 000079055 700__ $$0(orcid)0000-0001-9219-5420$$aAliaga-Lavrijsen, M. 000079055 700__ $$aCornejo, M.A. 000079055 700__ $$aJarzecki, A.A. 000079055 700__ $$aContel, M. 000079055 773__ $$g14 (2019), 1-11$$pChemMedChem$$tChemMedChem$$x1860-7179 000079055 8564_ $$s728211$$uhttps://zaguan.unizar.es/record/79055/files/texto_completo.pdf$$yPostprint 000079055 8564_ $$s21029$$uhttps://zaguan.unizar.es/record/79055/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000079055 909CO $$ooai:zaguan.unizar.es:79055$$particulos$$pdriver 000079055 951__ $$a2020-07-16-08:49:12 000079055 980__ $$aARTICLE