Titanocene Y and Vanadocene Y: Platinum Resistance-Breaking Cytotoxic and DNA-Targeting Anticancer Drug Candidates

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

“…Thus, we evaluated the effect of the novel chiral cyclopentadienyl oximato Ti(IV) compounds on cytotoxicity, cell adhesion and migration of the human androgen-independent prostate cancer PC-3. In addition and since some titanocene compounds (such as titanocene Y, titanocene Y*, titanocene T and heterometallic titanocene-gold compounds [14,20–30,33,34,36,37]) have shown to be very active against renal cancer both in vitro and in vivo , we evaluated the cytotoxicity of selected compounds in another three cell lines (human renal Caki-1, human colon DLD-1 and human triple negative breast MDA-MB-231 cancer cell lines). In order to assess the compounds’ selectivity for cancerous cells with respect to normal cell lines, they were also screened for their antiproliferative effects on the non-tumorigenic human embryonic kidney cells HEK-293T.…”

“…Thus, a plethora of modified titanium-based compounds have been synthesized and studied as potential antitumor agents, especially during the last decade [5,6,14,15,18–32]. Substituted titanocenes such as Titanocene Y [33,34] (Ti-Y, Fig. 1), Titanocene Y* [35,36] (Ti-Y*, bis-[(p-diethylaminobenzyl)cyclopentadienyl]titanium(IV) dichloride, Fig.…”

β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding

“…Compound 5 was previously reported, [28] and all other compounds have been fully characterised by 1 H NMR Scheme 1 Synthetic pathway a), b) and c) for bis(-diketonate)titanium compounds 1-31 and Budotitane. [16] spectroscopy, 13 Figure 4 and the structures adopt a mix of geometries either cis-trans-cis or cis-cis-trans with half or one molecule in the asymmetric unit cell. The crystallographic data is presented in Table S1-S2 (see SI).…”

“…High DNA-adduct levels were obtained at IC50 concentrations, indicating DNA is a target for these metallocene drugs. [13] Computational studies of Titanocene Y with doublestranded DNA have since shown, that after the loss of the two chloride ligands, the dicationic Titanocene Y coordinates strongly to a phosphate group. [14] In addition, hydrolysis and DNA studies of Cp2TiCl2 and Titanocene Y, with bis(4-nitrophenyl) phosphate (BNPP) have been studied (Figure 1).…”

Anticancer and Antibacterial Activity of Transition Metal Complexes

“…Likewise, Titanocene Y was able to induce apoptosis via the FAS receptor pathway . Promising results of Titanocene Y were shown in the induction of apoptosis in platinum‐resistant human colon and lung cancer cells by targeting DNA . This property showed that Titanocene Y was a potent cytotoxic component in second‐ or third‐line cancer therapy.…”