0000000001299501
AUTHOR
Jacob Fernández-gallardo
Auranofin and related heterometallic gold(I)-thiolates as potent inhibitors of methicillin-resistant Staphylococcus aureus bacterial strains.
A series of new heterometallic gold(I) thiolates containing ferrocenyl-phoshines were synthesized. Their antimicrobial properties were studied and compared to that of FDA-approved drug, auranofin (Ridaura), prescribed for the treatment of rheumatoid arthritis. MIC in the order of one digit micromolar were found for most of the compounds against Gram-positive bacteria Staphylococcus aureus and CA MRSA strains US300 and US400. Remarkably, auranofin inhibited S. aureus, US300 and US400 in the order of 150-300 nM. This is the first time that the potent inhibitory effect of auranofin on MRSA strains has been described. The effects of a selected heterometallic compound and auranofin were also stu…
Versatile synthesis of cationic N-heterocyclic carbene–gold(i) complexes containing a second ancillary ligand. Design of heterobimetallic ruthenium–gold anticancer agents
We describe a versatile and quick route to cationic gold(i) complexes containing N-heterocyclic carbenes and a second ancillary ligand (such as phosphanes, phosphites, arsines and amines) of interest for the synthesis of compounds with potential catalytic and medicinal applications. The general synthetic strategy has been applied in the preparation of novel cationic heterobimetallic ruthenium(ii)-gold(i) complexes that are highly cytotoxic to renal cancer Caki-1 and colon cancer HCT 116 cell lines while showing a synergistic effect and being more selective than their monometallic counterparts.
Heterometallic titanium–gold complexes inhibit renal cancer cells in vitro and in vivo
Following recent work on heterometallic titanocene-gold complexes as potential chemotherapeutics for renal cancer, we report here on the synthesis, characterization and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = S-C6H4-COO-) bound to gold(I)-phosphane fragments through a thiolate group ([(η-C5H5)2TiMe(μ-mba)Au(PR3)]. The compounds are more stable in physiological media than those previously reported and are highly cytotoxic against human cancer renal cell lines. We describe here preliminary mechanistic data involving studies on the interaction of selected compounds with plasmid (pBR322) DNA used as a model nucleic acid, and with s…
Heterometallic titanium–gold complexes inhibit renal cancer cells in vitro and in vivo † †This paper is dedicated to Prof. Roberto Sánchez-Delgado, great mentor and excellent friend, on the occasion of his 65th birthday. ‡ ‡Electronic supplementary information (ESI) available: Stability studies of the new compounds by NMR, UV-vis spectroscopy and MS spectrometry, crystallographic data for compound 6, DFT calculations for compounds 4–7, IC50 values in human renal cells at both 24 and 72 h, details on migration studies, TrxR inhibition studies for 3, 5 and AF at different times, inhibition studies of compound 5 against a panel of 35 protein kinases, effects of AF on MAPKAPK-3 in Caki-1 cells, effects of compound 3 in Caki-1 mouse xenografts. CCDC 1400886. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5sc01753j Click here for additional data file. Click here for additional data file.
Heterometallic compounds as anticancer agents demonstrating in vivo potential for the first time. Titanocene–gold derivatives: promising candidates for renal cancer.
Titanocene–gold complexes containing N-heterocyclic carbene ligands inhibit growth of prostate, renal, and colon cancers in vitro
We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)−N-heterocyclic carbene fragments through the thiolate group: [(η5 -C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold−N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both tita…
Organometallic Titanocene–Gold Compounds as Potential Chemotherapeutics in Renal Cancer. Study of their Protein Kinase Inhibitory Properties
Early–late transition metal TiAu2 compounds [(η-C5H5)2Ti{OC(O)CH2PPh2AuCl}2] (3) and new [(η-C5H5)2Ti{OC(O)-4-C6H4PPh2AuCl}2] (5) were evaluated as potential anticancer agents in vitro against renal and prostate cancer cell lines. The compounds were significantly more effective than monometallic titanocene dichloride and gold(I) [{HOC(O)RPPh2}AuCl] (R = −CH2– 6, −4-C6H4– 7) derivatives in renal cancer cell lines, indicating a synergistic effect of the resulting heterometallic species. The activity on renal cancer cell lines (for 5 in the nanomolar range) was considerably higher than that of cisplatin and highly active titanocene Y. Initial mechanistic studies in Caki-1 cells in vitro couple…
CCDC 977988: Experimental Crystal Structure Determination
Related Article: Yozane Hokai, Boruch Jurkowicz, Jacob Fernández-Gallardo, Nuruddinkodja Zakirkhodjaev, Mercedes Sanaú, Theodore R. Muth, María Contel|2014|J.Inorg.Biochem.|138|81|doi:10.1016/j.jinorgbio.2014.05.008
CCDC 1436326: Experimental Crystal Structure Determination
Related Article: Jacob Fernández-Gallardo, Benelita T. Elie, Mercedes Sanaú, María Contel|2016|Chem.Commun.|52|3155|doi:10.1039/C5CC09718E
CCDC 977989: Experimental Crystal Structure Determination
Related Article: Yozane Hokai, Boruch Jurkowicz, Jacob Fernández-Gallardo, Nuruddinkodja Zakirkhodjaev, Mercedes Sanaú, Theodore R. Muth, María Contel|2014|J.Inorg.Biochem.|138|81|doi:10.1016/j.jinorgbio.2014.05.008
CCDC 1436327: Experimental Crystal Structure Determination
Related Article: Jacob Fernández-Gallardo, Benelita T. Elie, Mercedes Sanaú, María Contel|2016|Chem.Commun.|52|3155|doi:10.1039/C5CC09718E
CCDC 1008332: Experimental Crystal Structure Determination
Related Article: Jacob Fernández-Gallardo, Benelita T. Elie, Florian J. Sulzmaier, Mercedes Sanaú, Joe W. Ramos, María Contel|2014|Organometallics|33|6669|doi:10.1021/om500965k
CCDC 1400886: Experimental Crystal Structure Determination
Related Article: Jacob Fernández-Gallardo, Benelita T. Elie, Tanmoy Sadhukha, Swayam Prabha, Mercedes Sanaú, Susan A. Rotenberg, Joe W. Ramos, María Contel|2015|Chemical Science|6|5269|doi:10.1039/C5SC01753J