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.
In Vitro and in Vivo Evaluation of Water-Soluble Iminophosphorane Ruthenium(II) Compounds. A Potential Chemotherapeutic Agent for Triple Negative Breast Cancer
A series of organometallic ruthenium(II) complexes containing iminophosphorane ligands have been synthesized and characterized. Cationic compounds with chloride as counterion are soluble in water (70–100 mg/mL). Most compounds (especially highly water-soluble 2) are more cytotoxic to a number of human cancer cell lines than cisplatin. Initial mechanistic studies indicate that the cell death type for these compounds is mainly through canonical or caspase-dependent apoptosis, nondependent on p53, and that the compounds do not interact with DNA or inhibit protease cathepsin B. In vivo experiments of 2 on MDA-MB-231 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (…
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 1008354: Experimental Crystal Structure Determination
Related Article: Malgorzata Frik, Alberto Martínez, Benelita T. Elie, Oscar Gonzalo, Daniel Ramírez de Mingo, Mercedes Sanaú, Roberto Sánchez-Delgado, Tanmoy Sadhukha, Swayam Prabha, Joe W. Ramos, Isabel Marzo, and María Contel|2014|J.Med.Chem.|57|9995|doi:10.1021/jm5012337
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